Therapy resistance and recurrence are irrefutably ascribed to the unique attributes of the cancer stem cell (CSC) population. Therefore, discerning the underlying mechanism is imperative in arbitrating a strategic therapeutic approach. In this study, we have observed the coexistence of neuron-like cell (NLC) subpopulations in different cancer cell lines. The NLC subset was further validated by transfection studies and was found to be positive for PSD-95. As a proof of concept, we have also demonstrated the transpiration of neurological phenomena such as long-term potentiation (LTP) and long-term depression (LTD) in cancer. We have utilized PMA drug and IL-13 cytokine to study LTD and LTP, respectively, and observed a correlation between the memory marker (GLUN2B) and stemness markers (CD95 and CD58). Moreover, the transcriptional protein pCREB, which plays a crucial role in memory formation, was found to influence CD44 protein levels. These findings suggest that the instigation of LTD can impair cellular memory and sensitize CSC to the metabolic inhibitor, 3Bromopyruvate. Furthermore, this study interfaces the neurobiology of cancer and nanomedicine, wherein we have used biomimetic nanocarriers for the active targeting of drugs and demonstrate their ability to augment therapeutic efficiency.

Infectious etiologies have previously been proposed as causes of both melanoma and non-melanoma skin cancer. This exploratory overview explains and presents the evidence for the hypothesis that a microorganism excreted in infected ruminant animal feces, Mycobacterium avium subspecies paratuberculosis (MAP), is the cause of some cases of cutaneous melanoma (CM). Occupational, residential, and recreational contact with MAP-contaminated feces, soil, sand, and natural bodies of water may confer a higher rate of CM. Included in our hypothesis are possible reasons for the differing rates and locations of CM in persons with white versus nonwhite skin, why CM develops underneath nails and in vulvar skin, why canine melanoma is an excellent model for human melanoma, and why the Bacille Calmette-Guérin (BCG) vaccine has demonstrated efficacy in the prevention and treatment of CM. The pathogenic mechanisms and etiologic aspects of MAP, as a transmittable agent underlying CM risk, are carefully deliberated in this paper. Imbalances in gut and skin bacteria, genetic risk factors, and vaccine prevention/therapy are also discussed, while acknowledging that the evidence for a causal association between MAP exposure and CM remains circumstantial.

The rapid progress in cancer treatment, along with the increase in cure and control rates, has led to the gradual acceptance of cancer as a chronic disease. Cancer treatment is comprehensive and long-term. However, cancer symptoms and treatment side effects can hinder patients’ quality of life and adherence to treatment, ultimately impacrefting their long-term survival. Acupuncture (AC) and electro-acupuncture (EA) have been widely used to treat various diseases. AC and EA have demonstrated their ability to relieve symptoms and side effects related to cancer treatment. The review provides a brief overview of the historical lineage and basic principles of AC treatment, as well as a detailed exploration of the mechanisms and clinical applications of AC and EA to relieve cancer symptoms and treatment side effects. AC and EA can play a therapeutic role by regulating systems of nervous, endocrine, immune and so on. Clinical studies have demonstrated that AC and EA can effectively relieve pain, postoperative ileus, and other symptoms. The safety of AC and EA has been tested worldwide. Furthermore, we discuss the challenges and future research directions for AC and EA in the field of cancer treatment.

Malignant pleural mesothelioma (MPM) is a malignant tumor of the pulmonary pleural tissue for which there is a lack of effective targeted therapy. In this study, moderate to high V-domain immunoglobulin T-cell activation suppressor (VISTA) expression levels were observed in most MPM clinical tumor samples. We prepared two high-affinity anti-VISTA monoclonal antibodies (mAbs) and generated two novel VISTA-targeted antibody-drug conjugates (ADCs) by conjugating anti-VISTA mAbs with the potent cytotoxic drug monomethyl auristatin E (MMAE). αV1-MMAE and αV2-MMAE showed potent killing effects to VISTA-positive cell lines in vitro, with half-maximal inhibitory concentration (IC₅₀) of nanomolar levels. αV1-MMAE and αV2-MMAE were also able to significantly induce apoptosis and cause G2/M phase arrest in VISTA-positive cells. In the VISTA-positive human MPM xenograft model, both αV1-MMAE and αV2-MMAE showed significant antitumor activity, led to a significant survival advantage compared to mice in the control group, and effectively induced apoptosis in the tumor tissues of mice. In conclusion, we demonstrated that the novel VISTA-targeted ADCs (αV1-MMAE and αV2-MMAE), especially αV1-MMAE, had potent killing effects against VISTA-positive MPM cells both in vitro and in vivo. Therefore, through further development, they may have the potential to become new drugs for the treatment of MPM.

Identifying mechanisms underlying cancer resistance to therapy is vital for advancing treatment strategies. Pathogenic mutations of homologous recombination repair (HRR) genes are known biomarkers for platinum (Pt)-based chemotherapy and poly ADP ribose polymerase inhibitors (PARPi) effectiveness. Yet, the dynamics of HRR reversion mutations, which may herald therapy resistance, are not fully elucidated. Addressing this gap, our study analyzed secondary HRR gene mutations in a comprehensive pancancer data set of approximately 13,000 patients who underwent targeted nextgeneration sequencing. We identified a subset of patients harboring secondary mutations, which were further categorized into three tiers based on their nature, and occur in the presence of a primary pathogenic mutation, notably in BRCA1, BRCA2, PALB2, and RAD51D genes. Here we show that secondary BRCA2 mutations, indicative of adaptive resistance, emerge post-Pt/Olaparib treatment. This challenges the prevailing notion that pathogenic HRR mutations uniformly predict therapeutic sensitivity, highlighting a nuanced genetic interplay that impacts treatment success. This investigation enriches our understanding of cancer’s adaptive mechanisms against therapy, suggesting a pivotal shift towards more personalized, dynamic treatment strategies. It underscores the imperative of adapting to cancer’s genetic evolution, aiming for a step ahead in the ongoing battle against this disease.