Aim: Neuroblastoma has a variable outcome depending on age, stage, and molecular pathology. Distant metastatic disease is the central feature of high-risk disease. Recommendations for irradiating persistent metastatic deposits with curative intent after systemic therapy vary. It is unclear to what extent this practice may improve local control or survival. This study systematically reviewed the evidence for skeletal metastatic site irradiation and made evidence-based recommendations for clinical practice.

Methods: We systematically reviewed the literature on radical radiotherapy of persistent metastases after chemotherapy. The aim was to determine whether a position could be taken regarding metastatic site irradiation in combined modality treatment protocols aiming for a cure and whether recommendations could be formulated.

Results: The initial search yielded 445 results. After the title and abstract review, 13 full papers were retrieved. Ten papers were found suitable for data extraction. One additional paper was identified. All 11 were graded as Centre for Evidence-Based Medicine Step 4 in quality; there was no high-level evidence. There are suggestions of benefit for skeletal site irradiation in high-risk neuroblastoma; however, there is no certainty, and it was not possible to recommend a particular treatment policy.

Conclusion: We recommend that consideration is given to a randomised evaluation of the benefits of radiotherapy to a limited number of residual post-induction-chemotherapy metastatic sites in good responders. This practice could be incorporated as an amendment to existing trials.

Advanced hormone receptor-positive breast cancer is one of the women’s most common malignant diseases and remains incurable despite recent therapeutic innovations. The dependence of hormone receptor-positive breast cancer on hormonal growth signals offers the possibility of inhibiting this signaling pathway using anti-hormonal therapy. Nevertheless, the development of resistance to antitumoral drugs remains a challenge. Molecularly-targeted substances significantly improve survival rates and (as in the case of cyclin-dependent kinase 4 and 6 inhibitors) are widely used in clinical practice and enhance endocrine therapy’s efficacy. Agents such as everolimus, alpelisib, and capivasertib target the phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin pathway, which is a promising approach to overcoming endocrine resistance. Novel therapies are being studied in numerous trials, and some already show significant benefits in survival rates. The development of new therapies to avert endocrine resistance is an urgent challenge in modern medicine. The following review will examine some promising therapeutic approaches.

Ovarian cancer (OC) is associated with poor outcomes and challenges scientists and clinicians. It is usually diagnosed in advanced stages when it is frequently aggressive, chemoresistant, and metastatic. The most prevalent form of OC is epithelial ovarian cancer (EOC), which displays significant heterogeneity, enhancing the difficulty in managing the disease. Several factors have been associated with the disease’s development and progression, especially those related to the tumor microenvironment (TME). Here, we highlight components of the ovarian TME in the disease development process, including pro-inflammatory pathways activated by interleukins, cytokines and chemokines, cancer-associated fibroblasts, tumor-associated macrophages, and epithelial-mesenchymal transition. We compiled evidence identifying TME factors promoting the development, chemoresistance, and metastasis, including cytokines, chemokines, growth factors, and tumor-associated cells. We identify potential targets for treatment and improving outcomes. These targets block or alter pathways associated with OC (especially EOC) progression.

The pathophysiology of skin cancer is complex, with multiple factors contributing to its development. The proactive treatment of skin cancer has been investigated in the form of chemoprevention of cutaneous malignancies in clinical trials. Chemoprevention is the use of natural or pharmacologic agents that prevent or reverse skin cancer development. Multiple trials have arisen over the past decades to explore the efficacy of specific agents to halt the progression of UV radiation damage. This comprehensive review article aims to assess clinical trials performed with chemopreventive agents for melanoma and nonmelanoma skin cancers. The following compounds were most often used in these trials: nicotinamide, retinoids, polyphenolic antioxidants, COX-2 selective inhibitors, non-steroidal anti-inflammatory drugs, difluoromethylornithine, and 5-fluorouracil. Many agents show promise in their ability to prevent nonmelanoma skin cancer formation, with few melanoma trials demonstrating efficacy. The chemoprevention efforts aimed at skin cancer are complex; current and future trials will be instrumental in identifying therapeutic agents that pose efficacy in halting cancer development and assessing whether long-term administration is tolerable.

Pancreatic cancer is an aggressive malignancy with increasing incidence. Pancreatic ductal adenocarcinoma (PDAC) accounts for > 90% of pancreatic cancer diagnoses, while other exocrine tumors are much rarer. In this review, we have focused on two rare cancers of the exocrine pancreas: adenosquamous carcinoma of the pancreas (ASCP) and pancreatic acinar cell carcinoma (PACC). The latest findings regarding their cellular and molecular pathology, clinical characteristics, prognosis, and clinical management are discussed. New genetic and transcriptomic data suggest that ASCP is related to or overlaps with the basal transcriptomic subtype of PDAC. These tumors are highly aggressive and driven by activated KRAS and MYC expression. Clinical outcomes remain poor and effective treatments are limited. PACC has no morphologic or genetic resemblance to PDAC and more favorable outcomes. Early stage PACC patients have improved survival with surgical resection and patients with advanced disease benefit most from platinum- or fluoropyrimidine-containing chemotherapy. Frequency of actionable genetic mutations is high in this disease and case reports suggest good outcomes when matched therapy is given. Dedicated clinical studies examining ASCP and PACC are limited and difficult to accrue. Further research is needed to define optimal clinical management for these rare diseases.

Nasopharyngeal carcinoma (NPC) has a distinct geographical prevalence in Southern China and Southeast Asia with a high overall survival rate (> 90%) in the early stage of the disease. However, almost 85% of patients suffer from the locally advanced disease with nodal metastasis at diagnosis. The overall survival rate would drastically drop to 63%. In addition to the generic tumor, nodal, and metastasis (TNM) staging, radiomic studies focusing on primary nasopharyngeal tumors have gained attention in precision medicine with artificial intelligence. While the heterogeneous presentation of cervical lymphadenopathy in locally advanced NPC is regarded as the same clinical stage under TNM criteria, radiomic analysis provides more insights into risk stratification, treatment differentiation, and survival prediction. There appears to be a lack of a review that consolidates radiomics-related studies on lymph node metastasis in NPC. The aim of this paper is to summarize the state-of-the-art of radiomics for lymph node analysis in NPC, including its potential use in prognostic prediction, treatment response, and overall survival for this cohort of patients.

Aim: Non-steroidal anti-inflammatory drugs are the most used analgesics for postoperative pain management. Aceclofenac is a newer phenylacetic acid derivative, and being a predominant cyclooxygenase-2 inhibitor, it has better gastrointestinal tolerability than diclofenac. The aim was to compare the efficacy and safety of aceclofenac and diclofenac in managing postoperative pain using the Face Legs Activity Cry Consolability (FLACC) score and a visual analog scale (VAS) following composite resection for oral cancer.

Methods: Seventy-six patients who underwent composite resection for oral cancer at a tertiary care hospital were randomly assigned to receive either injection of aceclofenac 150 mg or diclofenac 75 mg intramuscularly at 0, 12, 24, 36, 48, and 60 h postoperatively. The FLACC score was recorded at 2, 4, 8, 12, and 24 h, and the VAS score was recorded at 24, 36, 48, 60, and 72 h. Intravenous tramadol 100 mg was given as a rescue analgesic if the FLACC or VAS score was > 3. The patient satisfaction score was recorded at 72 h.

Results: There were 61 female and 15 male patients. Mean surgery durations in the aceclofenac and diclofenac groups were 450.00 ± 116.00 and 416.84 ± 130.63 minutes, respectively. Mean FLACC scores between the two groups were not significantly different. Patients receiving diclofenac had significantly lower mean VAS scores (P = 0.005) at 72 than at 24 h. There was no significant difference in mean VAS scores between groups. The amount of rescue analgesic required in both groups was similar (P = 0.34). At 72 h, 31.57% of patients graded their satisfaction as good in the aceclofenac group and 34.21% in the diclofenac group. Nausea and dyspepsia were common adverse effects in both groups.

Conclusion: Aceclofenac was as effective as diclofenac in reducing postoperative pain following composite resection for oral cancer. In individuals with a history of gastritis or peptic ulcer, aceclofenac can be an alternative to diclofenac.

Aim: Although treatment of lung cancer, one of the deadliest diseases worldwide, with immune checkpoint inhibitors (ICIs) has shown promising outcomes, these survival outcomes are only observed in a relatively small subset of lung cancer patients. In a previous study, we elucidated that the presence of human neutrophil peptide (HNP) 1, 2 and 3 in non-small cell lung cancerous (NSCLC) biopsies is associated with a clinical response towards treatment with PD-1/PD-L1 immune checkpoint inhibitors. Furthermore, HNP1 has shown in vitro an immune-activated function towards lung cancer cells, but the specific role of HNP1 in (lung) cancer is still unknown. The aim of this study was to provide a better understanding of HNP1 in an NSCLC microenvironment.

Methods: To gain better insights into the role of HNP1 on cancer growth and to unravel immune responses, in vitro (SILAC-labelled) A549/PBMC (from three healthy donors) cocultures were set up and treated/not treated with HNP1. After 5 days, both secretome and cellular analysis using mass spectrometry were performed on these cocultures. After protein identification in all different tested conditions, pathway analyses (MetaCore^TM) were performed to investigate the biological significance of HNP1 stimulation on the A549/PBMC cocultures. The proteomic outcomes were confirmed by multiplex ELISA for a proinflammatory cytokine panel (TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-12p70 and IL-18).

Results: A number of biological pathways and process networks were observed to be upregulated after treatment of the coculture with HNP1. HNP1 stimulation leads to an increase in pathways and proteins stimulating chemotaxis (including plasmin signaling, leucocyte recruitment, CCL2 and CXCL8 expression), proinflammatory cytokine secretion (including IL-1β, IL-6 and TNF-α), dendritic cell (DC) maturation, phagocytosis and antigen presentation, leading to a more efficient adaptive anti-tumoral immunity.

Conclusion: These results enhance our understanding of the role of HNP1 in the tumor microenvironment and suggest that HNP1 may be able to induce tumor necrosis by inducing prostimulatory immune responses.

Neuroblastoma is the most common extracranial solid tumor in children and comprises one-tenth of all childhood cancer deaths. The current clinical therapy for this deadly disease is multimodal, involving an induction phase with alternating regimens of high-dose chemotherapeutic drugs and load reduction surgery; a consolidation phase with more intensive chemotherapy, radiotherapy, and stem cell transplant; and a maintenance phase with immunotherapy and immune-activating cytokine treatment. Despite such intensive treatment, children with neuroblastoma have unacceptable life quality and survival, warranting preventive measures to regulate the cellular functions that orchestrate tumor progression, therapy resistance, metastasis, and tumor relapse/recurrence. Globally, active efforts are underway to identify novel chemopreventive agents, define their mechanism(s) of action, and assess their clinical benefit. Some chemoprevention strategies (e.g., retinoids, difluoromethylornithine) have already been adopted clinically as part of maintenance phase therapy. Several agents are in the pipeline, while many others are in preclinical characterization. Here we review the classes of chemopreventive agents investigated for neuroblastoma, including cellular events targeted, mode(s) of action, and the level of development. Our review: (i) highlights the pressing need for new and improved chemopreventive strategies for progressive neuroblastoma; (ii) lists the emerging classes of chemopreventive agents for neuroblastoma; and (iii) recognizes the relevance of targeting dynamically evolving hallmark functions of tumor evolution (e.g., survival, differentiation, lineage transformation). With recent gains in the understanding of tumor evolution processes and preclinical and clinical efforts, it is our strong opinion that effective chemopreventive strategies for aggressive neuroblastoma are a near reality.

Oncolytic viruses (OVs) are at the forefront of biologicals for cancer treatment. They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that, either as single agents or as part of combination therapies, are being evaluated in preclinical and clinical settings. As the field gains momentum, the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus, the tumor and the immune system, with the aim of rationally designing more efficient therapeutic interventions. Nowadays, the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus, but by its contribution as an immunostimulator, triggering the transformation of the immunosuppressive tumor microenvironment (TME) into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses. Here we review the immune mechanisms and host responses induced by ssRNA(-) (negative-sense single-stranded RNA) viruses as OV platforms. We focus on two ssRNA(-) OV candidates: Newcastle disease virus (NDV), an avian paramyxovirus with one of the longest histories of utilization as an OV, and influenza A (IAV) virus, a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.

The incidental discovery of pancreatic cysts in asymptomatic patients is on the rise due to the widespread use of cross-sectional imaging. The challenge in the management of pancreatic cysts is in distinguishing those with malignant potentials, like mucinous pancreatic cysts, from non-mucinous cysts that have negligible malignant potentials. Similarly, it can be difficult to identify mucinous cysts that harbour high-grade dysplasia or early cancer. This review focuses on the recent advances in detecting pancreatic cancer and cysts with premalignant potential.

Oligometastatic soft tissue sarcoma represents an intermediate state between localized and disseminated disease. Combination A combination of surgery, radiotherapy and systemic treatment significantly improves prognosis, with a 5-year overall survival as high as 50%. Due to the high prevalence of lung metastases, most of the surgical evidence is centered around lung metastasectomy. The decision to perform surgical metastasectomy remains dependent on optimal patient selection. Adequate post-surgical lung function, absence of extrapulmonary metastases, control of the primary tumor, and feasibility of achieving negative margins are major criteria for patients to undergo successful surgery. Adequate margins, longer disease-free interval, unilateral, limited number (≤ 2), metachronous and small (< 2 cm) pulmonary metastasis are some factors associated with improved survival. Radiotherapy, especially SBRT, is an effective treatment for disease control, and its use as (neo)-adjuvant therapy has shown promising results. However, studies comparing radiotherapy against surgery are missing and the efficacy of radiotherapy independent of surgery is not yet clear. Interventional radiology techniques such as percutaneous thermal ablation (PTA) or arterial embolization have also been described as potential treatment alternatives in candidates deemed not fit for surgery. Systemic treatment has traditionally consisted of an anthracycline (doxorubicin)-based regimen with the addition of ifosfamide in certain cases. Recent advances in systemic treatment include the use of targeted therapy and immunotherapy in (oligo)-metastatic STS. However, except for certain histologies, most STS subtypes are chemoresistant, and the response to systemic treatment is poor.

Aim: High-risk endometrial cancer has a higher risk of regional and distant recurrence. We sought to examine our institutional experience regarding the timing of adjuvant radiotherapy and local failure (LF), locoregional failure (LRF), distant failure (DF), and overall survival (OS).

Methods: We retrospectively reviewed a database of patients with high-risk endometrial cancer treated with sequential chemotherapy followed by adjuvant external beam radiation therapy (EBRT) with or without brachytherapy from 2012 to 2019.

Results: One hundred thirty-one patients were identified. The median age at diagnosis was 65 (range 32-81). The most prevalent FIGO stages were IIIB (28.2%, n = 37), IIIC1 (19.8%, n = 26), and IIIA (17.6%, n = 23). Of the patients, 29% (n = 38) had positive lymph nodes and 71% (n = 93) had negative lymph nodes. The most prevalent histology was endometrioid (71%, n = 93), serous (12.2%, n = 16), clear cell (9.2%, n = 12), and other (7.6%, n = 10). Moreover, 100% (n = 131) of the patients completed EBRT. The mean EBRT dose was 49.6 Gy (range 45-50.4). The median number of days between surgery and EBRT was 212.4 days (range 103-219). The mean brachytherapy dose was 14.7 Gy (range 12-30). The cumulative incidence of LF was 6.1%, LRF was 19%, DF was 19%, and the median survival was 33.4 months. For patients who completed EBRT 180 days after surgery, LRF (HR 3.55 [1.23-10.2], P = 0.013), LF (HR 1.91 [0.4-8.9], P = 0.429), DF (HR 0.91 [0.41-2], P = 0.806), and OS (HR 0.92 [0.33-2.6], P = 0.87).

Conclusion: In our cohort of patients with high-risk endometrial cancer treated with chemotherapy followed by radiotherapy, delaying RT was associated with an increased risk of LRF but no differences in DF or OS.

Glioblastoma (GBM) is one of the most immunosuppressive and heterogeneous tumors with limited treatment options. Most studies relied on treatment-experienced patient samples to elucidate the origins of tumor heterogeneity, introducing bias into the analysis. The analysis of samples from multifocal GBM patients, in which independent lesions arise from the same progenitor and undergo parallel evolution, enables the study of the natural evolution of GBM while removing the effect of therapy on the emergence of heterogeneity. This enables the identification of critical events in the evolution of GBM and the unbiased study of subtype progression, diversity, and invasive potential. The tumor microenvironment of GBM undergoes significant changes throughout tumor progression. Recent studies have highlighted the switch from an abundance of resident microglia-derived macrophages in earlier stages to the prevalence of blood-derived macrophages in later stages of GBM. There is conclusive evidence that these alterations cannot be viewed in isolation and that the tumor microenvironment co-evolves with tumor cells during cancer progression. Together with an increasingly hypoxic environment, this culminates in highly immunosuppressive conditions, resulting in a feedback loop further reinforcing evolutionary changes in the tumor. A new study now provides a unique look at the natural evolution of GBM, identifies critical events in its development, and has the potential to help improve the diagnosis and therapy of this deadly disease.

Aim: Cancer stem cells are cell populations that are essential in drug resistance and cancer metastasis. Some liver cancer cells exhibit the characteristics of cancer stem cells, and it is crucial to study the activities and interactions of drugs in these cells. Huh7 is a human liver cancer cell with stem cell biomarkers and is used with induced pluripotent stem cells to form various cancer organoids through encapsulation methods. Due to their ease of use without animal testing, bio-fabrication studies of cell-encapsulated models have gained importance in the pharmaceutical industry in recent years. This study aimed to biofabricate Huh7 human liver cancer stem cells by alginate encapsulation and test gemcitabine’s efficacy.

Methods: Huh7 cells were encapsulated with alginate (0.8% w/v) and fibronectin, and their viability was evaluated with 3.2 µM gemcitabine on days 1, 3, 6, 9, and 12. Furthermore, gene expressions of stem cell markers CD90 and AFP were evaluated in encapsulated Huh7 cells by qPCR. In addition, IL-6 secretion in the cell medium was measured by ELISA for the tumor microenvironment.

Results: Encapsulation of Huh7 cells was found to maintain their viability and stem cell properties for up to 12 days. In addition, alginate-encapsulated Huh7 cells were bio-fabricated to demonstrate long-term gemcitabine response. While the effect of the gemcitabine was evaluated in alginate-encapsulated Huh7 cells, CD90 and AFP mRNA levels were significantly reduced in the cells and IL-6 secretion was decreased in the tumor microenvironment.

Conclusion: This study demonstrated that bio-fabrication of alginate-encapsulated Huh7 cells is a novel approach for long-term drug testing in liver cancer models. Bio-fabricated alginate-encapsulated cancer stem cells may be a cheaper and faster method for the testing of many drugs.

Sentinel node biopsy (SNB) is considered the standard surgical procedure for detecting occult neck node metastasis in oral squamous cell carcinoma (OSCC) in many centers around the world. Due to the fact that this method removes and evaluates the first lymph node(s) reached by the lymphatic flow from the tumor area, this has raised the question of whether SNB could also be considered a therapeutic procedure by targeted lymphadenectomy instead of elective neck dissection (END). Compared to END, its safety and low morbidity have been established. However, the surgical management of the clinical node-negative (cN0) neck in T1/T2 oral carcinoma has been under ongoing debate due to the lack of randomized studies comparing SNB to END in terms of overall survival (OS), disease-free survival (DFS) and neck recurrence rates (NRRs). In the last years, two prospective randomized studies have proven with high-level evidence the noninferiority of SNB compared to END in terms of oncologic outcome while reducing costs and morbidity. In our opinion, SNB should be offered as the new standard therapeutic procedure in early OSCC.

Multiple myeloma (MM) is a disease of clonally differentiated plasma cells. MM is almost always preceded by precursor conditions, monoclonal gammopathy of unknown significance (MGUS), and smoldering MM (SMM) through largely unknown molecular events. Genetic alterations of the malignant plasma cells play a critical role in patient clinical outcomes. Del(17p), t(4;14), and additional chromosomal alterations such as del(1p32), gain(1q) and MYC translocations are involved in active MM evolution. Interestingly, these genetic alterations appear strikingly similar in transformed plasma cell (PC) clones from MGUS, SMM, and MM stages. Recent studies show that effectors of the innate and adaptive immune response show marked dysfunction and skewing towards a tolerant environment that favors disease progression. The MM myeloid compartment is characterized by myeloid-derived suppressor cells (MDSCs), dendritic cells as well as M2-like phenotype macrophages that promote immune evasion. Major deregulations are found in the lymphoid compartment as well, with skewing towards immune tolerant Th17 and Treg and inhibition of CD8+ cytotoxic and CD4+ activated effector T cells. In summary, this review will provide an overview of the complex cross-talk between MM plasma cells and immune cells in the microenvironment and the molecular mechanisms promoting progression from precursor states to full-blown myeloma.

Aim: Patients with muscle-invasive bladder cancer (MIBC) have a low survival rate, with a 5-year survival of approximately 45%, regardless of the treatment received. The risk of death within 5 years after radical cystectomy in patients with MIBC remains as high as 60%. Over 80% of patients with bladder cancer are over 65. Therefore, identifying prognostic correlates associated with radical cystectomy in older patients with MIBC could improve survival rates. In addition, radiotherapy and chemotherapy are particularly important as adjuvant treatments for MIBC patients undergoing radical cystectomy. Therefore, this study aimed to find risk factors for cancer-specific survival (CSS) and overall survival (OS) after radical cystectomy in elderly MIBC patients. The difference in survival between radiotherapy and chemotherapy was analyzed by Kaplan-Meier (K-M) curves to provide theoretical support for whether radiotherapy is recommended for such patients.

Methods: Patients 65 or older diagnosed with MIBC with radical cystectomy between 2004-2018 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. 2004-2015 patients were subjected to column line plot production and internal validation, and 2016-2018 patients were subjected to external temporal validation. A single-factor COX regression model was first used to screen for prognostic correlates. Then a multi-factor COX regression model was used to screen for independent risk factors. A nomogram was constructed by using independent risk factors. The accuracy and reliability of the nomogram were examined using calibration curves, consistency index (C-index), and area under subjects (AUC) as operational characteristic curves. Decision curve analysis (DCA) was performed to evaluate the clinical value of the prediction model.

Results: A total of 11,557 patients were included in this study, divided into training set (N = 4,712), validation set (N = 4,810) and external validation set (N = 2,035). Multivariate COX regression models showed that chemotherapy, radiotherapy, TNM stage, race, and age were independent risk factors for CSS and OS patients. We constructed a nomogram to predict CSS and OS in elderly MIBC patients undergoing radical cystectomy. The C-indexes were 0.692 (95%CI: 0.680-0.704) and 0.690 (95%CI: 0.678-0.702) for the CSS training and validation sets, respectively, and 0.674 for the OS training and validation sets (95%CI: 0.664-0.684) and 0.672 (95%CI: 0.662-0.682) for the OS training and validation sets, respectively. The C-index of the external validation set CSS was 0.731 (95%CI: 709-0.753), and that of OS was 0.721 (95%CI: 0.701-0.741), indicating that the nomogram prediction model has good discriminative power. The calibration curves and AUC also suggested that the nomogram had good accuracy and discrimination. In addition, the KM curves of propensity-matched pre- and post-radiotherapy showed that radiotherapy was detrimental to patient survival. Meanwhile, chemotherapy favored OS and short-term CSS but not long-term CSS.

Conclusions: We established a nomogram to predict the CSS and OS in elderly MIBC patients undergoing radical cystectomy. After internal cross-validation and external validation, the nomogram prediction model showed good accuracy and reliability, and the DCA results showed that the nomogram has good clinical value. In addition, this study gave good suggestions on whether radiotherapy or chemotherapy is necessary for radical cystectomy in elderly MIBC patients.

First-line systemic therapy with immune checkpoint inhibitors (ICIs) is currently the mainstream treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) that is not amenable to local therapy. However, the optimal treatment after discontinuation of ICIs is still unknown, and no large-scale analysis has been conducted in R/M SCCHN. In this narrative review, we summarize the treatment strategies available to continue ICI therapy using the currently available treatment modalities. After the administration of ICIs, unlike cytotoxic agents, the following responses are observed: durable response, pseudo-progressive disease, hyper-progressive disease, mixed response, immune-related adverse events (irAEs), and improved sensitivity to subsequent chemotherapy. Some patients show a durable response to ICIs and a good prognosis; however, many patients will require salvage therapy. We need to select the subsequent treatment according to the various responses unique to ICIs to obtain a durable response. For instance, there are reports on the effectiveness of reapplication of local therapy for a mixed response, retreatment with ICIs, and off-treatment in responsive cases complicated by irAEs. If a durable response can be maintained with ICI therapy, a long-term prognosis that cannot be obtained with conventional chemotherapy can be achieved.

Lymph node status of the neck is the most important prognostic factor in head and neck cancer. Neck dissection, which consists of the systematic excision of the neck nodes, represents the gold standard of surgical treatment in clinically positive necks. In cases in which metastases to lymph nodes of the neck are not detectable, the decision to perform an elective neck dissection depends on the stage and the site of the primary tumor. This narrative review focuses on the anatomical description and oncological role of a group of lymph nodes of the neck that historically has not been well defined. Over the years, several authors have described the groups of lymph nodes that lie where the facial vein crosses the mandible, but to date, no unique definition or a clear view of their oncological role has been proposed. Recently, the term “perimarginal nodes” was coined to refer to this group of lymph nodes, and emphasis was placed on the risk of leaving them undissected during neck dissection. This paper aims to provide a surgical-anatomical classification of these lymph nodes and describe their oncological role on the basis of a review of the relevant literature.

Despite our growing understanding of the genomic landscape of diffuse pleural mesotheliomas (DPM), there has been limited success in targeted therapeutic strategies for the disease. This review summarizes attempts to develop targeted therapies in DPM, focusing on the following targets being clinically explored in recent and ongoing clinical trials: vascular endothelial growth factor, mesothelin, BRCA1-associated protein 1, Wilms tumor 1 protein, NF2/YAP/TAZ, CDKN2, methylthioadenosine phosphorylase, v-domain Ig suppressor T-cell activation, and argininosuccinate synthetase 1. Although preclinical data for these targets are promising, few have efficaciously translated to benefit our patients. Future efforts should seek to expand the availability of preclinical models that faithfully recapitulate DPM biology, develop clinically relevant biomarkers, and refine patient selection criteria for clinical trials.

The incidence of nodal metastasis is quite common in well-differentiated thyroid cancer. However, its clinical significance is generally quite minimal. The adverse pathological features need to be recognized. The debate continues over prophylactic central compartment dissection. However, it needs to be re-evaluated in terms of complications of elective procedure. The extent of lateral neck dissection is standardized from level II through level V. Recurrent nodal disease is more likely to be persistent nodal disease. Appropriate preoperative imaging is very crucial. Surgery for recurrent disease needs to be considered based on nodal prognostic factors and location of the disease. The approach of using active surveillance and continuous monitoring is reasonable, especially for recurrence below 1 cm.

Breast cancer continues to be a difficult disease to treat due to high rates of metastasis. Metastasis to the brain presents a unique and often overlooked challenge. In this focused review, we discuss the epidemiology of breast cancer and which types frequently metastasize to the brain. Novel treatment approaches are highlighted with supporting scientific evidence. The role of the blood-brain barrier and how it may become altered with metastasis is addressed. We then highlight new innovations for Her2-positive and triple-negative breast cancer. Finally, recent directions for luminal breast cancer are discussed. This review serves to enhance understanding of pathophysiology, spark continued innovation, and provide a user-friendly resource through tables and easy-to-process figures.

Introduction: Patients with soft tissue sarcoma (STS) that present with metastasis at diagnosis have a dire prognosis. Within this patient population, we sought to assess: (1) demographic and clinical characteristics, (2) metastatic patterns, (3) treatment strategies, and (4) disease-specific survival (DSS).

Materials and Methods: The SEER database was queried to identify patients with histologically confirmed STS of the pelvis or extremity. Univariate and multivariate analysis was performed using the Cox proportional hazards model. Disease-specific survival (DSS) was analyzed using the Kaplan-Meier method.

Results: A total of 22,683 patients were retrieved, out of which 2,553 (11.3%) had metastasis at diagnosis. Leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), liposarcoma, synovial sarcoma, spindle cell sarcoma, and alveolar rhabdomyosarcoma (A-RMS) were the six most common STS presenting with metastasis. Among patients with metastasis, 53.7% and 33.2% of patients had primary tumors located in the lower limb and pelvis, respectively. Lung was the most common site of metastasis in all subtypes except A-RMS, in which bone metastases and lymph node (LN) predominated (85.2% and 62.1%, respectively). Chemotherapy and radiotherapy were associated with higher DSS (HR = 0.788 and HR = 0.755, respectively). Five-year DSS was below 20% in all tumor histologies. Two-year DSS for patients with synchronous lung and liver metastases was 28%.

Conclusion: Although the lung was the most common site of metastasis, metastatic patterns are highly variable depending on tumor histology. Metastatic A-RMS is most commonly presented with regional LN and bone involvement. Disease-specific survival remained poor for patients with metastatic disease at presentation regardless of (neo)-adjuvant radiotherapy or chemotherapy.

Ovarian cancer remains the most lethal gynecologic malignancy in the USA. For over twenty years, epithelial-mesenchymal transition (EMT) has been characterized extensively in development and disease. The dysregulation of this process in cancer has been identified as a mechanism by which epithelial tumors become more aggressive, allowing them to survive and invade distant tissues. This occurs in part due to the increased expression of the EMT transcription factor, SNAI1 (Snail). In the case of epithelial ovarian cancer, Snail has been shown to contribute to cancer invasion, stemness, chemoresistance, and metabolic changes. Thus, in this review, we focus on summarizing current findings on the role of EMT (specifically, factors downstream of Snail) in determining ovarian cancer aggressiveness.

Pleural mesothelioma (PM) is an aggressive malignancy of the pleural lining that typically arises secondary to asbestos exposure. With the advent of next-generation sequencing, major progress has been made in the molecular characterization of pleural mesothelioma over the past three decades. However, these advances have been largely unable to identify effective targeted therapies for PM. Additionally, there remains an absence of accepted gold-standard consensus for staging and treatment, which partly explains the overall poor outcomes in patients with PM. In recent years, genetic profiling of PM tumors has proved to be an effective tool in the diagnosis and prognosis of PM. Genomic sequencing has identified several potential targets for the development of novel therapeutics in PM. This review summarizes the progress in diagnosis, prognosis, and therapeutics derived by genomics and tumor profiling of PM tumors.

Malignant melanoma is believed to have the highest rate of cardiac metastasis of any cancer based on autopsy studies, but descriptions of clinical findings, diagnosis, and treatment remain lacking. In particular, the use of immunotherapy has been only sparingly described. We present eight cases of malignant melanoma treated at our institution. Four patients displayed symptoms, three were diagnosed on routine surveillance imaging, and one was diagnosed postmortem. Locations of cardiac tumors varied with all four chambers and septum involved between the cases. Six patients underwent genetic profiling: two patients had a CDKN2A variant detected in their cardiac tumor, one patient had a BRAF mutation, and one patient had an NRAS mutation. Six patients underwent immunotherapy with either anti-PD-1 and/or anti-CTLA-4 therapy. This report highlights the importance of considering cardiac melanoma in surveillance imaging and the use of immunotherapy for management.

As an emerging strategy in antitumor therapy, photodynamic therapy (PDT) has garnered significant attention in recent years for the treatment of various malignant tumors. This is due to its low side effects, superior spatial selectivity, and maximum preservation of normal tissue function. However, the hypoxic nature of tumors, continuous oxygen consumption, and microvascular damage associated with PDT treatment have impeded its development. Therefore, the focus of antitumor therapy has shifted towards enhancing the efficacy of PDT by addressing tumor hypoxia. The objective of this review is to assess and summarize the recent advancements in tumor treatment using synergistic therapy strategies (PDT+X, where X represents photothermal therapy, chemodynamic therapy, chemotherapy, immunotherapy, Photoacoustic therapy, etc.) that overcome hypoxia. Additionally, this review aims to outline the advantages and disadvantages of various collaborative methods for improving tumor hypoxia, while also discussing the challenges that lie ahead for future research.

Immunotherapy has shown promising results with improved progression-free survival and overall survival in lung cancer. However, novel immunotherapy could generate atypical response patterns, which is a big challenge for traditional imaging criteria. Radiomics, combined with artificial intelligence (AI), represents new quantitative methodologies that could serve as an additional imaging biomarker to predict immunotherapy benefits and assess responses to assist oncologists in decision-making in lung cancer treatment. This paper aims to review the latest advancement of AI-based radiomics applied to lung cancer patients receiving immunotherapy, focusing on the fundamentals of these approaches and commonly used techniques. We also address the hurdles in the AI and radiomic analysis pipeline to guide clinicians in approaching this new concept.

The development of uterine cervical cancer is primarily attributed to infection by high-risk human papillomaviruses (HR-HPVs). E5, E6 and E7, the three early oncoproteins of HR-HPVs, have been implicated in initiation and progression of cervical cancer. The intricate molecular mechanisms that orchestrate aberrant cellular transformations to establish carcinoma of the cervical epithelium following viral infections are poorly understood. Here, we discuss how deregulation of three major cell fate regulatory pathways, Hedgehog, Wnt and Notch, and cell survival strategies involving EGFR signaling and G1/S checkpoint contribute towards cervical cancer development and progression. Further exploration of protein interaction database has revealed several genes that are involved in cervical cancer initiation and progression, and the two crucial "driver” genes, MYC and CTNNB1 (β-catenin), have been identified as major players in protein-protein interaction network. GSK3β emerged as the key mediator of crosstalk between Hedgehog, Wnt and Notch signaling pathways. GSK3β regulates cytoplasmic stabilization and nuclear translocation of β-catenin, which further impacts the expression of MYC, critical for cell cycle progression. Collectively, our analyses suggest that combinatorial therapeutic targeting of these proteins may be more effective in blocking cervical cancer initiation and progression.

Radiotherapy is an integral part of the management of head and neck cancers, both in radical and adjuvant settings. Traditionally, similar radiation dose and fractionation schedules have been used based on tumor stage with variable outcomes indicating “one size does not fit all”. In the era of precision medicine, though we have achieved physical precision with technological advancements, we have yet to attain biologic precision. In the current review, we have highlighted the different aspects of precision oncology such as hypoxia targeting, radiomics and radiogenomics, radiobiologic targeting, and big data. The review also discusses various potential therapeutic targets and approaches in head and neck cancer management that might help to increase radiosensitization, which in turn increase survival, and quality of life. This can be incorporated into the armamentarium of radiation oncology in all the phases of radiation planning, from diagnosis to treatment to the prognosis and management of long-term side effects. Biologic precision can be applied in the clinic to provide individualized, personalized treatment in the future.

Background: Cervical cancer is a significant public health concern worldwide, and human papillomavirus (HPV) is the leading cause of this disease. While there have been some studies on the prevalence of HPV in Kazakhstan, the country faces unique challenges in preventing and treating HPV-related diseases, including limited resources, a lack of awareness about HPV, and cultural attitudes toward sexual health. This research article aims to provide a comprehensive overview of HPV genotype distribution in Astana, Kazakhstan, for the last five years.

Methods: A cross-sectional study was performed from 2018 to 2022. Study population: Kazakhstani women referring to “Olympus laboratories network” settings for HPV testing age 18-64. AmpliSens® Real-Time PCR kits for HPV genotyping 14 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) were performed.

Results: This study revealed the increasing trend in HR-HPV prevalence among women for five sequential year periods. As a result, approximately 43% of women referred to the HPV testing were HR-HPV positive, with the most prevalent type being HPV 16 (20%), followed by HPV types 31, 52, 51.

Conclusion: By examining the latest research on HPV and cervical cancer in Kazakhstan, we hope to contribute to developing effective public health policies and interventions to help reduce these diseases' burden in this country. Furthermore, the database will be established for future large-scale studies after vaccination implementation.

Adiponectin, an adipokine synthesized by adipose tissue, has garnered significant attention in biomedical investigations. Research on its implications suggests that reduced adiponectin levels in the bloodstream might serve as a potential predisposing factor for several types of cancers, including gastric cancer. Although many studies on adiponectin levels in gastric cancer patients have been reported, its predictive role as a biomarker remains controversial. Moreover, the significance of adiponectin receptor expression as a prognostic factor in gastric cancer tissues varies across different research studies, and the precise mechanism by which adiponectin influences the initiation and advancement of gastric cancer remains to be fully elucidated. Furthermore, the anti-inflammatory and postoperative anti-infective effects of adiponectin are worth further investigation. Based on existing studies, it is commonly suggested that in the presence of low adiponectin levels, the stomach might be vulnerable to stimulation or damage from certain carcinogens, promoting gastric cancer development and progression. Considering its complex systemic effects and high serum concentration, adiponectin might serve as a homeostasis regulator and not necessarily as an anti-cancer factor. In this review, we explore the current research available on adiponectin in relation to gastric cancer and discuss its role and corresponding receptors involved in gastric cancer.

Objective: The ideal time interval between induction chemotherapy and surgery and the impact on cancer mortality in patients with mesothelioma remains unclear.

Methods: We queried the National Cancer Database (2004-2017) for patients with favorable prognostic factors considered for surgery. Immediate surgery was performed within 3 months following the start of induction chemotherapy, while delayed surgery was defined as surgery performed later than 3 months. We compared both groups to those who did not have an operation despite being surgical candidates, as well as to those who were treated with surgery only. Overall mortality was assessed using Cox proportional hazard models adjusting for covariates.

Results: A total of 4,294 patients were included, with the majority of patients undergoing induction chemotherapy followed by no surgery (3,370, 78%). The proportion of patients undergoing both immediate and delayed surgery increased over the last decade, but delayed surgery continued to be more common. There were no significant differences in baseline characteristics between the immediate and delayed surgery groups. Higher comorbidity scores were significantly associated with an increased risk of death on multivariable analysis, but the timing of surgery was not. This held true with a sensitivity analysis using 6 months as the definition of delayed surgery.

Conclusions: This study shows that delaying surgery following induction chemotherapy does not compromise overall survival in patients with mesothelioma.

Aim: For many years, systemic treatment of metastatic Renal Cell Carcinoma (mRCC) was based on sequential targeted agent monotherapies. In this real-life case series, we evaluated easily accessible clinical factors useful for disease course prediction.

Methods: We exploited patients' clinical pathological characteristics and systemic treatment outcomes in a real-world population of 365 mRCC patients who received sequential monotherapies in the targeted therapy era, and we identified an early progressors subpopulation, resistant to first-line VEGFR-TKI monotherapy in less than 6 months.

Results: Early progressors (n = 124) show a far worse OS compared with patients progressing beyond the sixth month of therapy (13.5 vs. 44.8 months, P-value < 0.0001, HR = 0.41, 95%CI: 0.29-0.53). However, these patients did not show far worse performance in second and third-line settings compared to first-line responders. In the univariate analysis, IMDC risk class, sarcomatoid features, and Systemic Inflammation Index (SII) were correlated with first-line therapy Progression-Free Survival (PFS1). In multivariate analysis, variables correlated with first-line outcome were IMDC risk class, histotype, and number of metastatic sites at the diagnosis.

Conclusion: Real-world data can contribute to developing easy-to-use prognostic factors associated with refractory disease that could support clinicians in identifying the most appropriate treatment strategy for each patient.

A variety of indications have been published regarding the use of percutaneous thermal ablation for treating tumors of the musculoskeletal system, including bone and soft tissue lesions, benign and malignant lesions, and primary and metastatic tumors. In the appropriately selected patient, the advantages of percutaneous thermal ablation include decreased morbidity, decreased cost, and shorter hospitalization stays compared to surgery. The number of different thermal ablation modalities is increasing, and each modality has its advantages and disadvantages. Studies directly comparing the effectiveness of the various thermal ablation modalities are sparse, however, so the choice of ablation modality often depends on availability, user preference, and local expertise. Although the list of uses for percutaneous thermal ablation is ever-expanding, in this article, we will discuss the two most well-established indications, which are palliation of pain attributed to bone and soft tissue metastases and local control of oligometastatic disease. Numerous clinical trials have shown percutaneous thermal ablation to be an effective method of palliating pain due to bone and soft tissue metastases and of achieving local control in the setting of oligometastatic disease with low rates of complication.

Brain metastasis in colorectal cancer is a rare occurrence with poor prognosis and limited treatment options. This case report presents a unique and previously unreported case of brain metastasis in a patient with dMMR (DNA mismatch repair-deficient) colorectal cancer. The patient, a 70-year-old male, initially presented with abdominal pain and was diagnosed with moderately differentiated adenocarcinoma of the right colon. Following surgical resection and adjuvant chemotherapy, the patient developed cognitive decline and was found to have a metastatic lesion in the left temporal lobe. Immunohistochemical analysis revealed MSH2 positivity and MSH6, MLH1, and PMS2 negativity, indicating dMMR status. Further genetic testing showed wild-type Kras, Nras, and Braf, and high tumor mutational burden (TMB). The patient was subsequently treated with pembrolizumab immunotherapy, resulting in a significant improvement of symptoms and a reduction in the size of brain metastasis. This case highlights the rarity and challenging management of brain metastasis in colorectal cancer, particularly in the context of dMMR tumors. The successful use of immunotherapy in this case provides valuable insights into the potential efficacy of immune-based treatments for dMMR colorectal cancer with brain metastasis, underscoring the need for further research in this field.

Ovarian cancer is the leading cause of gynecologic cancer death in the United States. Most ovarian cancer patients are diagnosed with advanced-stage disease, which poses a challenge for early detection and effective treatment. At present, cytoreductive surgery and platinum-based chemotherapy are foundational for patients with newly diagnosed ovarian cancer, but unfortunately, most patients will recur and die of their disease. Therefore, there is a significant need to seek innovative, novel approaches for early detection and to overcome chemoresistance for ovarian cancer patients. The microbiome, comprising diverse microbial communities inhabiting various body sites, is vital in maintaining human health. Changes to the diversity and composition of the microbial communities impact the microbiota-host relationship and are linked to diseases, including cancer. The microbiome contributes to carcinogenesis through various mechanisms, including altered host immune response, modulation of DNA repair, upregulation of pro-inflammatory pathways, altered gene expression, and dysregulated estrogen metabolism. Translational and clinical studies have demonstrated that specific microbes contribute to ovarian cancer development and impact chemotherapy’s efficacy. The microbiome is malleable and can be altered through different approaches, including diet, exercise, medications, and fecal microbiota transplantation. This review provides an overview of the current literature regarding ovarian cancer and the microbiome of female reproductive and gastrointestinal tracts, focusing on mechanisms of carcinogenesis and options for modulating the microbiota for cancer prevention and treatment. Advancing our understanding of the complex relationship between the microbiome and ovarian cancer may provide a novel approach for prevention and therapeutic modulation in the future.

The identification of HER2-low metastatic breast cancer as a novel subgroup with therapeutic implications underscores the intricacies in breast cancer classification. This subset, comprising 45%-60% of breast cancer cases, presents a challenge due to its heterogeneous nature, characterized by varying HER2 protein expression levels. This heterogeneity complicates diagnosis and treatment decisions. The advent of trastuzumab deruxtecan (T-DXd), a second-generation antibody-drug conjugate (ADC), instills renewed hope for HER2-low breast cancer patients, having demonstrated effectiveness in clinical trials. The article also explores the evolution of HER2 testing guidelines, notably the 2023 ASCO/CAP guidelines that acknowledge the potential benefits of HER2-targeted therapies for this subgroup. In summary, this article emphasizes the significance of collaborative efforts between Pathologists and Oncologists in the era of precision medicine. It also highlights the potential for innovative, tailored therapies for HER2-low breast cancer, promising enhanced treatment outcomes and a broader range of therapeutic options.

Aim: Heterogeneity of glioblastoma (GB) cells significantly contributes to tumor resistance against temozolomide (TMZ) and the development of disease relapse. Multiple molecular mechanisms are involved in this process, yet the contribution of proteoglycans (PGs) remains unknown. This study aimed to investigate the potential involvement of PGs (both at core proteins and polysaccharide chains) in the heterogeneity and TMZ resistance of GB cells.

Methods: Seven human GB cell lines were characterized for TMZ sensitivity, cell phenotypic traits, gene expression for glucocorticoid receptor (GR, NR3C1), PG core proteins- and heparan sulfate (HS) biosynthesis-related genes and content of their chondroitin sulfate (CS) and HS chains.

Results: Although the studied cell lines have similar proliferation rates, they significantly differ in their migration activity, clonogenicity, and TMZ resistance (IC₅₀ 8.51-369.59 µM in the line of U343, LN215, HS683, U87, LN71, LN405, LN18), creating a specific phenotype for each cell line. Some PGs (NG2/CSPG4, CSPG5, and versican) contributed to the molecular heterogeneity of these cells being cell line-specifically expressed in all cell lines, which also differed in terms of the CS/HS content. Transcriptional activity of the HS metabolic system was low in these GB cell lines, expressing mainly EXT1/2 and NDST1/2, while expression levels of sulfotransferases and SULF2 were cell line-specific. TMZ resistance of these cells was correlated with the expression of stem-cell marker CD44 (+3.5-fold, r = 0.73) and GR (-3-fold, r = -0.81). TMZ treatment of the resistant (LN405) and sensitive (LN215) cells resulted in complex changes in cell migration as well as NG2/CSPG4 expression and CS/HS content.

Conclusion: Differential expression of PGs and CS/HS content contribute to the heterogeneity of GB cells, and CD44 and NR3C1 might be informative biomarkers for TMZ resistance.

Background: In stage IV breast cancer, surgical resection of the primary tumor was traditionally performed solely to palliate symptoms such as bleeding, infection, or pain. The ongoing discussion has shown that there are many research gaps in the current literature and differences in clinical practice. Thus, this systematic review and meta-analysis was designed to evaluate how primary tumor resection (PTR) affects the overall survival (OS) of patients with stage IV breast cancer. Method: A thorough literature search was completed using different databases (PubMed, Google Scholar, Scopus, ScienceDirect, and Cochrane Library) to find papers contrasting PTR with no PTR. The quality of research articles was evaluated using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale (NOS). Review Manager 5.4 was used to determine how much demographic and clinical factors contribute to heterogeneity through subgroup and meta-regression analysis. Results: Data derived from 44 observational studies (OS) and four randomized controlled trials (RCTs) including 227,889 patients were analyzed. Of all cases, 150,239 patients were included in the non-PTR group, and 70,795 patients in the PTR group (37 observational studies and 4 randomized control trials). The pooled outcomes of four RCT studies (Hazard Ratio (HR) = 1.03, 95%CI: 0.67-1.58; I² = 88%; P < 0.0001; chi-square 24.57) favor non-PTR. While pooled outcomes of 43 observational studies showed PTR significantly improved OS (HR = 0.66, 95%CI: 0.61-0.71; I² = 87%; P < 0.00001; chi-square 359.12). Additionally, subgroup analysis that compared PTR with non-PTR in patients with stage IV breast cancer for progression free-survival (HR = 0.89, 95%CI: 0.62-1.28; P = 0.03; I² = 71%) and locoregional progression-free survival (LPFS) (HR = 0.33, 95%CI: 0.14-0.74; P = 0.0004; I² = 87%) was found to be significant favoring the PTR group. Distant progression-free survival (DPFS) had a non-significant relationship (HR = 0.42, 95%CI: 0.29-0.60; P = 0.12; I² = 53%), while overall, there was a significant relationship (HR = 0.49, 95%CI: 0.32-0.75; P < 0.00001; I² = 90%). Subgroup analysis revealed that PTR is beneficial in patients with bone metastasis (HR = 0.83, 95%CI: 0.68-1.01; P = 0.01; I² = 56%), with one metastatic site (HR = 0.75, 95%CI: 0.63-0.59; P = 0.006; I² = 62%), but not in patients with positive margins (HR = 0.84, 95%CI: 0.67-1.06; P = 0.07; I² = 61%), negative margins (HR = 0.61, 95%CI: 0.59-0.63, P = 1.00; I² = 0%). Most of the patients in PTR and non-PTR groups belonged to white compared to other ethnic groups. Overall, observational studies were of high quality, while RCTs were of low quality. Conclusion: The current research suggests that PTR may be discussed as a possible option.

Aim: Cancer-related deaths are primarily caused by lung cancer around the world. The prognosis and burden of lung cancer must be improved by identifying novel biomarkers for diagnosis and treatment. In non-small cell lung cancer (NSCLC), the platelet isoform of phosphofructokinase 1 (PFKP) has been identified as a tumor-promoting oncogene. The current study examined the specific role that PFKP plays in NSCLC tumorigenesis, as well as the underlying mechanism.

Methods: A lung cancer dataset was obtained from the TCGA in order to examine the expression of PFKP. Using the Kaplan-Meier Plotter website, we calculated the overall survival (OS) along with the recurrence-free survivals (RFS) curves with high and low levels of PFKP in lung cancer. The mechanism by which zinc finger protein 148 (ZNF148) regulated PFKP/PD-L1 levels in NSCLC was investigated through chromatin immunoprecipitation (ChIP), qRT-PCR, and western blotting. In order to uncover ZNF148's function in NSCLC, subsequent functional studies included CCK-8, colony formation, and Transwell, along with glycolysis assays. Student’s T-test was conducted for data analysis with GraphPad Prism 9.0.

Results: The expression of PFKP in NSCLC was increased, and it was linked to worse outcomes. This increased expression of PFKP in NSCLC was induced by ZNF148. Silencing ZNF148 remarkably dampened NSCLC cell proliferation, invasion, and glycolysis capacities. According to a mechanistic study, ZNF148 regulates the PFKP/PD-L1 axis, which promotes NSCLC tumorigenesis.

Conclusion: It has been established that ZNF148-induced PFKP is key to the proliferation, invasion, and glycolysis abilities of NSCLC cells by regulating PD-L1 expression. Therefore, the ZNF148/PFKP/PD-L1 axis could be a potential biological signature and target for NSCLC diagnosis and treatment.