Cancer Biology & Medicine最新文献

Melanoma, the most aggressive form of skin cancer, remains a significant clinical challenge due to the high metastatic potential and drug resistance. This review explores the pivotal roles of angiogenesis and vasculogenic mimicry in melanoma progression and treatment resistance. Angiogenesis, driven primarily by VEGF/VEGFR signaling, is critical for tumor sustenance but is often insufficient under hypoxic conditions, prompting melanoma cells to adapt by forming vascular-like structures (i.e., vasculogenic mimicry). These structures enable melanoma cells to mimic endothelial functions and are linked to increased metastasis and poor prognosis. Molecular drivers, including VE-cadherin, EphA2, and hypoxia-inducible factors, have been identified as key regulators of these processes. Current anti-angiogenic agents have limited efficacy in advanced/metastatic melanoma due to tumor plasticity and the interplay between angiogenesis and vasculogenic mimicry. The review highlights the need for therapeutic strategies targeting both mechanisms, emphasizing the importance of combination treatments to overcome resistance. Future research should aim to elucidate the molecular underpinnings of angiogenesis and vasculogenic mimicry to improve melanoma management and patient outcomes.

Objective: This study aimed at exploring the effects of the epigenetic regulator, chidamide, on reprogramming the immunosuppressive tumor microenvironment in small cell lung cancer (SCLC), particularly the roles in macrophage polarization and angiogenesis. The therapeutic efficacy of combining chidamide with the anti-angiogenic agent, anlotinib, for refractory SCLC was also evaluated.

Methods: RNA sequencing and functional validation were performed to assess chidamide's effects on macrophages. Signal transducer and activator of transcription 4 (STAT4)-mediated transcriptional activation of CCL2 was confirmed with ChIP-qPCR. The synergistic efficacy of chidamide in combination with anlotinib was tested in preclinical models.

Results: Chidamide enhanced macrophage infiltration and induced macrophage polarization toward the anti-tumor M1 phenotype. Mechanistically, chidamide upregulated CCL2 via STAT4 transcriptional activation, thereby reshaping the tumor immune microenvironment (TIME). Combining chidamide with anlotinib synergistically suppressed tumor growth and remodeled the immunosuppressive TME in SCLC in vivo.

Conclusions: Chidamide reshaped the SCLC TIME by activating STAT4/CCL2, thus driving M1 macrophage polarization and enhancing anti-tumor immunity. Our findings highlight coordinated TIME-targeted therapy as a translatable strategy to overcome therapeutic resistance in SCLC and provide a rationale for clinical trials examining epigenetic and anti-angiogenic therapeutics combinations.

Objective: Large-scale CRISPR screens have identified essential genes across cancer cell lines, but links between tumor functional properties and specific dependencies require investigation to reveal the mechanisms underlying dependencies and broaden understanding of targeted therapy.

Methods: We selected 47 breast cancer cell lines from the Cancer Cell Line Encyclopedia (CCLE) with multi-omics data including gene dependency; somatic mutations; copy number alterations; and transcriptomic, proteomic, metabolomic, and methylation data. We established a dependency marker association (DMA) analytic pipeline by using linear regression modeling to assess associations between 3,874 representative gene dependencies and multi-omics markers. Additionally, we conducted non-negative matrix factorization clustering, to stratify breast cancer cell lines according to gene dependency features, and investigated cluster-specific DMAs.

Results: We interpreted valuable DMAs according to two primary aspects. First, dependencies associated with gain-of-function alterations revealed addiction to lactate transporter SLC16A3, thus suggesting a promising therapeutic target. Second, dependencies associated with loss-of-function alterations included synthetic lethality (SL), collateral SL, and prioritized metabolic SL, encompassing paralog SL (e.g., IMPDH1 and IMPDH2), single pathway SL (e.g., GFPT1 and UAP1), and alternative pathway SL (e.g., GPI and PGD). DMA analysis of the two clusters with divergent dependency signatures demonstrated that cluster1 cell lines exhibited extensive metabolism with mitochondrial protein dependencies, whereas cluster2 displays enhanced cell signaling, and reliance on DNA replication and membrane organelle regulators.

Conclusions: We established a DMA analysis pipeline linking the gene dependencies of breast cancer cell lines to multi-omics characteristics, thus elucidating the underpinnings of tumor dependencies and offering a valuable resource for developing novel precision treatment strategies incorporating relevant markers.

Objective: The aim of the current study was to identify independent prognostic factors, evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups, and define adjuvant chemotherapy-sensitive populations.

Methods: A retrospective analysis of 168 AAC patients undergoing curative pancreaticoduodenectomy (2011-2020) was performed. Cases were classified into intestinal (28.0%), pancreatobiliary (30.4%), and mixed subtypes (18.5%) per NCCN (v2.2025) criteria. Independent prognostic factors for AAC patients were identified through uni- and multi-variable Cox proportional hazards modeling and subgroup analyses were stratified by age range, gender, differentiation, T stage, N stage, BVI, TDs, and PNI.

Results: The pancreatobiliary signature (HR = 2.884, P < 0.001) and BVI (HR = 2.330, P = 0.001) were independent poor prognostic factors. Adjuvant chemotherapy improved overall survival (OS) in the following AAC patients: T3-T4 stage (HR = 0.485, P = 0.050); N1-N2 stage (HR = 0.365, P = 0.008); and TD-positive (HR = 0.401, P = 0.026). The median OS increased from 22.3-51.3 months with adjuvant chemotherapy in TD-positive patients (P = 0.019). TD positivity conferred a worse prognosis in BVI-negative subgroups (OS: HR = 3.840, 95% CI: 2.058-7.166, P < 0.001; and progression-free survival (PFS): HR = 2.950, 95% CI: 1.550-5.617, P = 0.002).

Conclusions: The pancreatobiliary signature and BVI constitute critical high-risk pathologic features in AAC. TD status identified high-risk cohorts, thus enabling postoperative risk-stratified treatment strategies. In patients negative for pancreatobiliary signature or BVI, TD positivity predicted significantly worse survival.

Objective: Cervical cancer remains a global health challenge with substantial disparities between countries. High-quality colposcopy is essential for cervical cancer prevention, yet training opportunities remain inadequate worldwide. We developed the Intelligent Digital Education Tool for Colposcopy (iDECO) to address training gaps and evaluated the effect across diverse international settings.

Methods: Six pre-post interventional training programmes were conducted in China, Mexico, and Mongolia from December 2024 to May 2025. A total of 369 trainees from 87 centers participated in a 3-week online training programme using iDECO, a bilingual web-based platform featuring authentic colposcopy cases, gamified learning pathways, and personalized analytics. The primary outcomes included colposcopy competence in general assessment, colposcopic findings, diagnostic accuracy, and management decisions. The secondary outcomes focused on participant feedback and satisfaction.

Results: Of 369 participants who completed pretests, 333 (90.24%) completed post-training assessments. Significant improvements were observed across all competency domains. Diagnostic accuracy increased with an odds ratio (OR) of 1.72 (95% CI: 1.60-1.86) with the greatest gains in high-grade lesion identification [OR = 2.27 (95% CI: 1.94-2.64)]. Squamocolumnar junction visibility and transformation zone type assessments improved with ORs of 1.41 (95% CI: 1.31-1.51) and 1.87 (95% CI: 1.73-2.01), respectively. Biopsy decision-making accuracy also showed significant improvement [OR = 2.09 (95% CI: 1.91-2.29)]. International participants showed lower baseline performance but achieved the greatest improvements. Greater than 85% of participants rated the training highly satisfactory and 83.56% preferred intelligent training over traditional methods.

Conclusions: iDECO-based training significantly improved colposcopy competence across diverse international settings with high user satisfaction. These findings support the potential for worldwide implementation of intelligent digital training tools to address colposcopy training gaps and contribute to the elimination of cervical cancer.