Medical Oncology最新文献

Gastric cancer remains a significant global health challenge, ranking as the 5th most common cancer worldwide with high mortality rates. Despite advances in diagnostic and therapeutic approaches, the prognosis for advanced gastric cancer remains poor due to its invasive nature and the lack of effective targeted treatments. The Hippo-YAP/TAZ signaling pathway, originally discovered in the fruit fly Drosophila melanogaster, has emerged as a critical regulator of cell proliferation, apoptosis, and organ size. Dysregulation of this pathway is increasingly implicated in gastric tumorigenesis. This pathway governs the activity of transcriptional co-activators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), through a core kinase cascade involving MST1/2 (Mammalian Ste20-like kinase 1/2), LATS1/2 (Large tumor suppressor kinase 1/2), and scaffold proteins such as SAV1 (Salvador homolog 1). Aberrations in the Hippo pathway have led to unchecked nuclear localization and transcriptional activity of YAP/TAZ, driving oncogenic gene expression that promotes cell survival, metastasis, and resistance to apoptosis. This review focuses on the molecular mechanisms underlying the dysregulation of the Hippo-YAP/TAZ signaling pathway in gastric cancer. It explores the crosstalk between Hippo-YAP/TAZ signalling and other oncogenic pathways, including Wnt/β-catenin and PI3K/Akt, as well as the influence of tumour microenvironmental factors such as hypoxia and extracellular matrix stiffness on pathway activation. Additionally, emerging therapeutic strategies targeting YAP/TAZ-TEAD interactions and upstream regulators are discussed, offering potential avenues for improving gastric cancer outcomes in diagnosis and treatment.

CD3 bispecific antibodies (BsAbs) targeting delta-like ligand 3 (DLL3) have emerged as promising candidates in cancer immunotherapy by enabling T-cell-mediated tumor lysis. A critical unmet need is to establish structural correlates of their preclinical activity and clinical efficacy to guide rational drug optimization. This study systematically characterized three clinical-stage CD3×DLL3 BsAbs, Tarlatamab (AMG757), BI764532 and HPN328, via structural modeling, T-cell activation assays, cytokine profiling, and tumor cytotoxicity tests. Preclinical data were further correlated with clinical trial outcomes to verify the predictive value of in vitro models. Preclinical data demonstrate a strong correlation with clinical outcomes, confirming that in vitro assays can reliably predict therapeutic response. Notably, structural features including immune synapse (IS) distance and epitope binding are tightly correlated with efficacy and safety. HPN328 exhibited the most potent T-cell activation and tumor killing activity, which aligned with its clinical confirmed complete response rate (cORR) of 50% in small cell lung cancer. BI764532 demonstrated a balanceed efficacy (ORR 18% in SCLC), while Tarlatamab achieved an ORR range of 13-40% across clinical trials. IS distance and epitope binding are strongly correlated with efficacy and safety of DLL3-targeted BsAbs, providing a critical framework for optimizing T-cell engager design in cancer immunotherapy.

Prostate cancer (PCa) is one of the most prevalent malignant tumors among men globally, with limited treatment options, especially in cases that progress to castration-resistant prostate cancer (CRPC). Identifying novel molecular targets and effective therapeutic strategies is crucial for improving patient outcomes. In this study, we identified serum and glucocorticoid-regulated kinase 1 (SGK1) as a potential target of the trifluoromethylquinoline derivative TKL007. A series of in vitro assays, including CCK-8, colony formation, Transwell migration and invasion assays, and flow cytometry, were performed to systematically evaluate the anti-tumor effects of TKL007 on the PC3 and LNCaP prostate cancer cell lines. Western blot analysis revealed that TKL007 significantly inhibited the activation of the PI3K/AKT signaling pathway. Further transfection experiments confirmed that SGK1 expression levels regulate the activity of the PI3K/AKT pathway, suggesting that SGK1 may modulate this signaling axis. In vivo xenograft experiments in nude mice demonstrated that TKL007 effectively inhibited tumor growth without causing significant toxicity. Taken together, these results suggest that TKL007 exerts anti-prostate cancer effects by downregulating SGK1 protein levels and inhibiting the PI3K/AKT pathway, providing a new candidate molecule and theoretical foundation for targeted therapy.

The aims of this study were to investigate the binding of platelets to colorectal cancer (CRC) cells, platelet activation by CRC cells, and determine the effect of platelets and platelet releasate containing extracellular vesicles on CRC cell proliferation, migration and invasion following aspirin pretreatment. Platelets from healthy individuals were pretreated with aspirin before co-incubation with CRC cells. Platelet activation by CRC cells was analysed by flow cytometry and the binding of platelets to CRC cells investigated using immunofluorescence microscopy. Platelet releasate containing extracellular vesicles was generated by centrifugation. The effect of platelets and platelet releasate on CRC cell proliferation was investigated using carboxyfluorescein succinimidyl esterand dimethylthiazol-carboxymethoxyphenyl-sulfophenyl-tetrazolium assays. Migration and invasion were examined using Transwell assays. HCT15 and HCT116 CRC cells activated platelets, with higher numbers of CRC cells activating more platelets, however aspirin was unable to inhibit platelet activation. Platelets are also able to bind to HCT15 and HCT116 cells. Platelets and platelet releasate did not affect HCT15 and HCT116 proliferation, however, aspirin directly inhibited the proliferation of both cell lines. Platelets and platelet releasate significantly increased the migration and invasion of HCT116, but not HCT15 cell lines. Platelets adhere to and are activated by CRC cells lines, with aspirin unable to inhibit this activation. CRC proliferation was not affected by platelets, however the effect on cancer cell migration and invasion was dependent upon the cell line, suggesting the effects of platelets and platelet releasate containing extracellular vesicles may be patient specific. The inhibitory effect of aspirin on colorectal cancer proliferation is a direct effect on the cancer cell and independent of platelets and extracellular vesicles.

Covalent organic frameworks (COFs) represent a rapidly expanding class of porous crystalline materials with exceptional potential in cancer diagnosis and therapy. Their ordered π-conjugated backbones, tunable pore architectures, and abundant functional sites provide unique advantages for drug loading, controlled release, and biointerfacing. Unlike conventional porous carriers, COFs exhibit intrinsic optical, electrical, and chemical properties that enable them to act both as delivery scaffolds and as active therapeutic platforms. Recent advances demonstrate their integration into drug delivery systems, photodynamic therapy (PDT), photothermal therapy (PTT), biosensing, and bioimaging. In cancer sensing and imaging, nanoscale COFs improve probe stability, enhance detection sensitivity, and enable responsive diagnostic platforms with reduced signal quenching. Furthermore, COFs can stabilize or directly function as photosensitizers and photothermal agents, thereby facilitating multimodal, imaging-guided therapeutic interventions. Despite these advances, key challenges remain, including scalable synthesis, long-term biocompatibility, precise drug-release control, and overcoming tumor heterogeneity. This review highlights emerging strategies to optimize COF stability, pore design, and functionalization, while exploring their potential applications across oncology. Finally, perspectives on clinical translation underscore the importance of interdisciplinary approaches to position COFs as next-generation platforms for precision cancer medicine, addressing urgent needs in early detection, therapeutic resistance, and metastasis management. Finally, the unique properties of COFs make them promising applicants for improving therapeutic products in cancer treatment.

Oral Squamous Cell Carcinoma (OSCC) is the most aggressive oral cancer type, with minimal survival rates resulting from metastases and disease recurrence. Early detection and innovative treatment approaches are required to limit metastases and improve survival rates. Dysregulated signaling affects a behavioral change in OSCC tumors, with alterations observed in tumor cell growth, proliferation, resistance to death etc. Aberrant signaling also plays an essential role in OSCC metabolic conditioning, helping tumors adapt to diverse host tissue microenvironments. Multiple miRNAs regulate signaling cascades in OSCC by controlling the expression of receptors, effectors and regulator genes. Therefore, the expression of specific miRNA in OSCC tumors can serve as diagnostic indictors as well as critical predictors for disease progression. In this review, we catalog miRNAs in OSCC with specific emphasis on their role in modulating signaling pathways associated with metabolic reprogramming.

Paclitaxel being an effective treatment for ovarian cancer, presents one of the most critical toxicities; peripheral neuropathy (PN), a debilitating side effect that might limit continuation of chemotherapy. Vitamin B was found to significantly improve PN and Gabapentin is debatably used in chemotherapy induced peripheral neuropathy (CIPN). The aim of this study was to assess the efficacy of vitamin B prophylaxis in reducing the severity of CIPN, particularly in diabetic patients with the need for Gabapentin as additional therapy and the potential impact on disease response. A clinical trial of 146 adult ovarian cancer patients received Paclitaxel for 18 weeks; randomly allocated into two arms: One arm received vitamin B prophylaxis before starting Paclitaxel and other received upon CIPN. Gabapentin was given upon aggravation of CIPN. This study showed a significant reduction in CIPN grade over time, with fewer patients progressed to higher grades in prophylactic versus non-prophylactic group, extended to significant improvement in CIPN in prophylactic versus non-prophylactic diabetic patients. Gabapentin was more significantly required in non-prophylactic versus prophylactic group. A significant correlation was found between dose modification due to CIPN and CA125 status. Finally, a significant difference in PFS between prophylactic and non-prophylactic group was found at the end of the study. These results reinforce the potential role of vitamin B prophylaxis in improving patient outcomes through significantly reducing CIPN severity and minimizing the risk of dose reductions, thereby contributing to better disease response. Trial registration number: NCT07191587, date of registration: 09/24/2025, retrospectively registered.

The anti-tumor clinical effect of traditional Chinese medicine gecko is very prominent. A novel anti-tumor protein component F2 was isolated and purified from geckos by our group, and the aim of this study was to investigate its antitumor effects in vitro and in vivo and its mechanism of action by inhibiting angiogenesis. The proliferation of cells was determined by colony formation assay and MTT assay. The apoptosis of A549 cells was detected by flow cytometry, and the gene expression changes of cells was analyzed by RNA-seq technology. An H22 tumor-bearing mouse model was prepared, the tumor tissue was analyzed by CD31 immunohistochemical staining. The expression levels of target proteins were detected by Western blot. The proliferation of tumor cells A549 and BEL-7402 was significantly inhibited by F2, but the growth of normal cells L02 was not affected. F2 induces apoptosis in A549 cells and inhibits its migration. RNA-seq results showed that F2 significantly inhibited MAPK signaling pathway in A549 and BEL-7402 cells, and the related genes MEK2 and ERK were significantly down-regulated. The zebrafish thrombus model test showed that the extract of gecko has a significant inhibitory effect on thrombus formation in zebrafish. F2 showed a tumor inhibition rate of 42.24% in mice. A decrease in blood vessels around the tumor and in the tumor tissue was observed. The treatment resulted in a significant down-regulation of VEGF and p-ERK expressions, while a significant up-regulation of p-JNK. In conclusion, F2 has significant antitumor activity. One of its mechanisms of action is to suppress angiogenesis in tumor tissue and surrounding tissues by inhibiting the VEGF/ERK/MAP signaling pathway.

Lung adenocarcinoma (LUAD), the predominant non-small cell lung cancer (NSCLC) subtype, faces major clinical challenges including poor prognosis and acquired drug resistance. This study integrates multi-omics analyses with in vitro functional validation experiments to systematically elucidate the molecular regulatory mechanisms of hyaluronan receptor (RHAMM/CD168) in LUAD development and its potential clinical translational value. Bioinformatics analysis based on public databases such as TCGA and GEO revealed that CD168 mRNA expression was significantly higher in LUAD tumor tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis and multivariable Cox regression models confirmed that high CD168 expression was independently associated with significantly shorter overall survival (OS) and progression-free survival (PFS) after adjusting for confounding factors such as age, gender, and clinical stage. Moreover, high CD168 expression correlated with altered immune cell infiltration patterns and changes in immune checkpoint molecule expression, suggesting that CD168 may play a crucial role in modulating the immune-suppressive tumor microenvironment and affecting responses to immunotherapy. Functional experiments demonstrated that silencing CD168 significantly inhibited cell proliferation, migration, and invasion in LUAD cell lines (A549 and H1299), and promoted apoptosis, confirming its oncogenic function. Bioinformatics analysis constructed the "lncRNA (CYTOR)-miRNA (hsa-let-7c-5p)-CD168" regulatory axis, wherein CYTOR may function as a ceRNA to sequester hsa-let-7c-5p, thereby alleviating miRNA-mediated suppression of CD168. Furthermore, Western blot analysis revealed that silencing CD168 decreased the phosphorylation levels of ERK and MEK, suggesting that CD168 promotes LUAD progression in association with MAPK/ERK signaling pathway activity. In summary, CD168 may promote LUAD progression by reshaping the immunosuppressive microenvironment and enhancing malignant behavior, establishing it as a prognostic biomarker and a potential therapeutic target, particularly for immunotherapy combinations.

Cisplatin resistance severely limits the efficacy of chemotherapy for cervical cancer (CC), and its molecular mechanisms remain incompletely understood. While epigenetic alterations such as DNA methylation are recognized as important contributors, the upstream regulatory networks, particularly the role of long non-coding RNAs (lncRNAs), are still unclear. This study aimed to explore novel mechanisms influencing cisplatin resistance in cervical cancer. Cisplatin-resistant CC cells (HeLa and SiHa) were established. A comprehensive approach employing mRNA and lncRNA microarrays, RT-qPCR, methylation-specific PCR (MSP-PCR), chromatin immunoprecipitation, luciferase reporter assays, RNA pull-down, RNA immunoprecipitation, cellular functional assays, and a mouse subcutaneous xenograft tumor model was utilized. The study found that Kallikrein 10 (KLK10) expression was significantly downregulated in cisplatin-resistant CC cells due to promoter hypermethylation mediated by DNA methyltransferase 1 (DNMT1). LncRNA microarray analysis revealed that TMPO-AS1 was the most significantly upregulated lncRNA in resistant cells. Functional assays confirmed that TMPO-AS1 promoted cisplatin resistance, proliferation, migration, and invasion of CC cells. Mechanistically, TMPO-AS1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-140-5p, thereby relieving its inhibitory effect on DNMT1 mRNA, upregulating DNMT1 expression, enhancing KLK10 promoter methylation, and leading to its silencing. In vivo experiments further demonstrated that silencing TMPO-AS1 inhibited tumor growth. This study unveils a novel TMPO-AS1/miR-140-5p/DNMT1/KLK10 regulatory axis that plays a critical role in cisplatin resistance in CC, providing a potential therapeutic target for overcoming chemoresistance.