F-Box and WD repeat domain-containing 7 (FBXW7) is a key tumor suppressor and substrate-recognition component of the Skp1-Cullin-F-box E3 ubiquitin ligase complex, responsible for targeting several crucial oncogenic proteins for proteasomal degradation. It plays a significant role in preventing the accumulation of pro-oncogenic substrates, thereby maintaining cellular homeostasis. Mutations or inactivation of FBXW7 disrupt these processes, leading to the stabilization of oncogenic proteins such as c-Myc, Notch, myeloid cell leukemia 1, and cyclin E, which drive malignant transformation in several cancers, including hematological malignancies such as T-cell and B-cell acute lymphoblastic leukemia. These mutations contribute to resistance to apoptosis, dysregulated proliferation, and poor prognosis, highlighting FBXW7 as a critical factor in leukemia pathogenesis and a promising therapeutic target. Here, we review FBXW7’s structure and function, its key substrates in leukemia, and therapeutic strategies that restore its function or target the oncogenic pathways it regulates. Advances in genome-wide CRISPR screenings and proteomics have further illuminated FBXW7’s involvement in multidrug resistance, positioning it as a biomarker and therapeutic target for improving leukemia treatment outcomes.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, initially developed to regulate cell cycle progression, have recently been recognized as potent immunomodulatory agents in cancer therapy. Accumulating evidence indicates that these inhibitors can modulate key immune cells, including T cells, natural killer cells, and macrophages, thereby enhancing their antitumor functions. By arresting cell cycle progression in both tumor and immune cells, CDK4/6 inhibitors create an immune-permissive microenvironment that facilitates more effective immune-mediated tumor eradication. In addition, these inhibitors may help overcome immune resistance mechanisms, providing a strong rationale for their combination with immune checkpoint inhibitors to amplify antitumor responses. Despite these promising findings, the specific mechanisms through which CDK4/6 inhibitors enhance immune responses, as well as their potential applications in breast cancer, remain areas of active investigation. A deeper understanding of their immunomodulatory effects is essential for developing novel combination therapies that could significantly improve the efficacy of cancer immunotherapy. This review synthesizes the latest evidence on the immunomodulatory effects of CDK4/6 inhibitors, highlighting their potential to augment antitumor immunity and exploring future directions for their clinical application.

Homologous recombination deficiency (HRD) affects genomic stability and has potential as a biomarker for the effectiveness of poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors. However, the clinical and molecular profile of HRD in non-small cell lung cancer (NSCLC), particularly in the Chinese population, remains poorly characterized. Based on the next-generation sequencing data of 158 Chinese NSCLC patients, we analyzed the HRD scores of mutations in homologous recombination repair (HRR) genes and dissected the correlation between HRD state and programmed death-ligand 1 (PD-L1) expression. Alterations in HRR genes were observed in 8.9% of the patients, with ATM and BRCA2 being the most commonly affected genes. HRD-high (HRD-H) status was significantly associated with advanced disease stage (≥III) and lung squamous cell carcinoma (LUSC). Transcriptomic analysis revealed distinct gene expression profiles between HRD-H and HRD-low (HRD-L) subgroups, with HRD-H tumors exhibiting predominantly downregulated genes. While EGFR mutations occurred at similar frequencies across HRD status, TP53 mutations were significantly enriched in HRD-H cases. HRD-H status correlated with higher PD-L1 positivity in NSCLC overall, but not within the lung adenocarcinoma (LUAD) subgroup in our cohort. The Cancer genome atlas analysis showed higher PD-L1 protein expression in HRD-H LUAD, but not in LUSC. Kyoto Encyclopedia of Genes and Genomes analysis identified enrichment of complement and coagulation cascades, ABC transporters, and bile secretion pathways in HRD-H tumors, suggesting links to immune evasion and drug resistance. This study elucidates the genomic landscape of HRD in Chinese NSCLC patients and provides insights into its potential clinical utility for therapeutic targeting. Our findings suggest that integrated HRD scoring may guide the application of PARP inhibitors and immunotherapy in specific NSCLC patient subgroups. Further prospective clinical studies are needed to validate the predictive value of HRD scoring in NSCLC treatment and to optimize patient selection strategies.

Prognosticating survival in palliative cancer patients has been a longstanding challenge. While different tools and approaches may ease prognostication, biological variability limits their accuracy. Assessment of physical status is important for prognostication, along with evaluating the degree of systemic inflammation and patient-reported symptom burden. The distribution of survival was examined among palliative cancer patients with different functional status (Eastern Cooperative Oncology Group Performance Status), inflammation-related markers (modified Glasgow prognostic score [mGPS]), and self-reported symptom intensities (the eleven-point numeric rating scale [0 - 10]). Physical status and biomarkers of systemic inflammatory responses yielded important prognostic information in patients with advanced cancer. Among 147 hospitalized patients, median survival was longer for those continuing anti-cancer treatment, those with better functional status, and those with normal levels of C-reactive protein and/or albumin. Regarding the functional status categories, patients with PS 2 exhibited the widest range of survival. All categories, except PS 4, included patients with actual survival of almost 1 year or more. In terms of inflammatory markers, the widest survival range was observed among patients with mGPS 0. All categories included patients with actual survival of more than half a year, and mGPS 0 and 1 included patients with survival of more than one and a half years. No statistically significant differences in survival were identified between patients with mild and higher intensities of the symptoms under investigation. A wide range of survival outcomes at the group level makes prognostication for individual patients particularly challenging.

The traditional paradigm of gene expression dysregulation emphasizes log-fold differential expression, with differentially expressed genes presumed to play key roles in relevant biological processes. In cancer, where normal tissue and tumors occupy non-overlapping regions in gene expression space, we propose an alternative and broader framework based on differentially expressed only-tumor genes (T-genes) and non-differentially dysregulated only-normal genes (N-genes). N-genes exhibit expression intervals found exclusively in normal samples, while T-genes display intervals exclusive to tumor samples. These N- and T-genes serve as markers that can be combined into small gene panels capable of perfectly discriminating between normal and tumor tissues. In most cases, these panels highlight biologically significant properties, such as altered glutamine metabolism in tumors. We provide an inventory of perfect gene panels for 12 cancer types, with potential applications in diagnostics and immunotherapy. Significance: Highly specific and sensitive combinatorial gene panels for the identification of 12 types of solid tumors in humans were derived from RNA sequencing expression profiles reported by The Cancer Genome Atlas network (https://www.cancer.gov/ccg/research/genome-sequencing/tcga). The corresponding software is available at the GitHub repository https://github.com/gabriel-gil/GenePan. This study revisits the concept of cancer-related gene expression dysregulation by introducing N-genes and T-genes as novel dysregulation patterns that can be leveraged in diagnosis, tumor classification, and therapeutic interventions.

The limitations of conventional cancer therapies, such as low selectivity and significant side effects, necessitate innovative approaches. This study proposes a pioneering self-theranostic strategy using magnesium-28 (Mg-28) alone, enabling simultaneous diagnosis, therapy, and treatment monitoring. Exploiting the elevated Mg ion demand in cancer cells, Mg-28 selectively targets Mg-dependent enzymes (e.g., DNA/RNA polymerases, hexokinase, telomerase) within intracellular organelles, such as the nucleus and mitochondria, without requiring biochemical carriers or nanoparticles, as in recent methods. A theoretical model based on the Mg-uptake coefficient predicts selective Mg-28 accumulation in tumors following intravenous administration. The Mg-28 decay chain—progressing through Aluminum-28 to stable Silicon-28—delivers highly localized irradiation through beta particles, Auger electrons, and recoil ions to critical intracellular structures, while simultaneously disrupting essential Mg-dependent enzymes. This results in a dual mechanism of radiotherapy and multi-enzyme inactivation. Simulations of linear energy transfer, radiation range, and absorbed dose show that nanogram-scale amounts of Mg-28 can deliver 60-400 Gy to tumors ranging from 0.03 mg to 500 g, suggesting potent cytotoxicity across a broad range of tumor sizes and stages. This potential is grounded in the universal metabolic reliance of cancer cells on Mg. Moreover, gamma emissions from Mg-28 and its daughter isotopes support early tumor detection and real-time treatment monitoring, enhancing therapeutic precision. As the first proposed single- isotope theranostic approach leveraging Mg dependency, this innovative strategy provides a robust foundation for future pre-clinical and clinical investigations aimed at validating its therapeutic efficacy, pharmacokinetics, and biosafety—thereby inaugurating a novel hypothesis for cancer therapy.

Despite the improved clinical outcomes resulting from the use of sorafenib, the development of resistance mechanisms continues to undermine its treatment efficacy. Recent studies have implicated the role of a phospholipid mediator, platelet-activating factor receptor (PAFR) pathway, and extracellular vesicles known as microvesicle particles (MVP) in influencing cellular behavior and the efficacy of therapeutic agents. In this study, we determined the impact of the PAFR pathway and the acid sphingomyelinase (aSMase), which is required for the biogenesis of MVP, on sorafenib-induced effects on lung cancer growth and MVP release. Using A549 and H1299 non-small cell lung cancer (NSCLC) cell lines, we showed that sorafenib treatment reduced cell viability in a dose and time-dependent manner. Notably, sorafenib also enhanced MVP formation in both NSCLC cell lines. This MVP release was significantly attenuated by pharmacologic inhibition of the PAFR pathway through the WEB2086 compound and the aSMase inhibitor, imipramine, indicating the involvement of the PAFR and aSMase in sorafenib-induced MVP biogenesis. Moreover, co-treatment with imipramine enhanced the cytotoxic effects of sorafenib, suggesting that targeting MVP-associated pathways may improve sorafenib response. Collectively, these findings offer mechanistic insight into how sorafenib modulates MVP release and supports the therapeutic potential of combining tyrosine kinase inhibitors with agents that disrupt MVP biogenesis in NSCLC.

Metastatic urothelial carcinoma, the most common subtype of advanced bladder cancer, remains associated with poor outcomes and limited treatment options despite systemic therapies. Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has shown significant improvements in progression-free and overall survival in platinum- and immunotherapy-pretreated patients, as demonstrated in the EV-201 and EV-301 trials. In this report, we present a case of a patient who had previously received platinum-based neoadjuvant chemotherapy and experienced disease progression under nivolumab maintenance therapy but subsequently achieved a complete response in a short period with EV treatment. EV has emerged as a valuable treatment alternative in this aggressive disease, where survival expectations are generally poor. However, questions remain regarding which patients benefit most from the treatment and whether the response is correlated with nectin-4 expression levels.

Malignant biliary tract obstruction (MBTO) is most commonly associated with primary hepatobiliary and pancreatic malignancies. Here, we present a rare case of a 65-year- old female who developed obstructive jaundice, which initially raised suspicion for hepatobiliary carcinoma. Cross-sectional imaging, including computed tomography and magnetic resonance imaging, revealed hepatic lesions, and endoscopic retrograde cholangiopancreatography demonstrated a malignant biliary stricture. Histopathological analysis of a liver biopsy unexpectedly confirmed metastatic urothelial carcinoma (UC). Further evaluation with cystoscopy, prompted despite the absence of urinary symptoms, identified a small bladder mass, which was biopsy- proven as the primary UC. UC typically metastasizes to lymph nodes, lungs, or bones, and isolated liver involvement causing MBTO is exceptionally uncommon. This case underscores the importance of maintaining a broad differential diagnosis in patients with malignant biliary obstruction, as atypical metastatic patterns can mimic more common hepatobiliary cancers and delay appropriate management.

The progression of rapidly growing teratomas in pregnancy may be influenced by hormonal and genetic factors. The current report is about a unique case involving a mature teratoma with rapid growth characteristics, yet it did not lead to any complications throughout pregnancy of a primigravida. The benign mature teratoma was identified via antenatal ultrasound during the first trimester. In this case, the patient experienced no adverse effects, and the size of the ovarian teratoma showed a gradual increasing trend during pregnancy without resulting in any complications. In summary, mature teratoma is a benign tumor with a good prognosis, and if fetal distress is detected, cesarean section should be recommended.

A 62-year-old male with newly diagnosed advanced-stage Hodgkin lymphoma (HL) developed life-threatening gastrointestinal (GI) complications during brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone chemotherapy. He presented with chemotherapy-induced enteritis and jejunal ileus, followed by severe GI bleeding requiring two consecutive laparotomies and segmental jejunal resections. Histology revealed ulcerative jejunitis without signs of lymphoma infiltration. His medical course was further complicated by acute renal failure requiring dialysis. Although the patient temporarily stabilized with intensive care management, he subsequently developed Candida sepsis. At the time of submission, his outcome remains uncertain. This case underscores a rare but serious occurrence of GI toxicity associated with intensive chemotherapy for HL.