Clinical & Translational Oncology最新文献

Peritoneal metastases represent the second most frequent site of dissemination in gastrointestinal stromal tumors (GIST), after the liver. Although associated with a worse prognosis than hepatic metastases, survival outcomes in peritoneal GISTosis are superior to those seen in peritoneal dissemination of other sarcomas or epithelial tumors. First-line treatment should always consist of tyrosine kinase inhibitors (TKIs), based on molecular profiling. In patients who achieve response, cytoreductive surgery may be considered aiming for complete macroscopic resection and improved oncologic outcomes. Evidence from large retrospective series supports this strategy, with reported 5-year overall survival rates of up to 80% and disease-free survival rates of approximately 30-35% in carefully selected cases. Conversely, surgery offers limited benefit in progressive disease. Therefore, surgical intervention should be performed between 6 and 12 months of TKI therapy, once tumor biology has been assessed. Decision-making must occur within multidisciplinary teams at experienced centers, integrating oncologic response, resectability, and patient condition to guide individualized treatment.

Background: Endometrial cancer (EC) is a common gynecological tumor. Insulin resistance (IR) increases the risk of EC. However, the common molecular basis between the two remains unclear. This study aims to screen the common differential expression genes (DEGs) between the two diseases and construct a prognostic risk model.

Methods: We obtained gene expression profiles and clinical information of patients with IR and EC from GEO and TCGA datasets. We performed differential analysis to discover the shared DEGs between IR and EC. Subsequently, the interactions among overlapping DEGs, along with their biological functions and genetic mutations in EC, were comprehensively analyzed via protein-protein interaction (PPI) network, function enrichment analyses, and genetic mutation analyses. Then, machine-learning algorithms were employed to figure out genes significantly associated with survival. For clinical application, we constructed a prognostic risk model and also compared tumor-infiltrating immune cells (TIICs) and genetic mutation between high- and low-risk groups. Finally, we screened one of the most important markers in the prognostic signature to investigate its expression-prognosis pattern, biological function, and underlying mechanism.

Results: Our analysis identified 20 co-upregulated genes and 32 co-downregulated genes of IR and EC. In addition, the two subnetworks and the top 20 top genes were obtained through PPI analysis, while the construction of extracellular matrix and immune response were the most enriched functions of DEGs. Filtered by random forest, gradient boosting machine, and extreme gradient boosting, six upregulated markers (ACTL8, WNT7A, CTSV, MMP9, CNIH2, and PLAUR) and four downregulated markers (COL6A6, MYOC, PHLDB1, and FIBIN), were defined as the characteristic genes for the prognosis of EC patients. The risk prediction model constructed by these ten genes had good predictive value in prognosis of EC patients and was related to immune regulation and genetic mutation. ACTL8 was further studied as the most significant marker among 10-gene signature. The correlation between the upregulation of ACTL8 and the poor prognosis of EC patients suggested its carcinogenic effect, which was correlated to its regulation of cilium movement.

Conclusion: Our findings suggest that there are common molecular profiles between IR and EC. IR-related prognostic model represents an excellent prognosis predictor and immune-related biomarker, which can be applied to risk stratification and precise treatment of EC patients with IR.

Cancer progression and treatment failure are driven not only by tumor-intrinsic alterations but also by dynamic interactions within the tumor microenvironment (TME). Epithelial-mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) represent two interlinked mechanisms that promote tumor invasion, metastatic dissemination, stemness, immune evasion, and resistance to therapy. EMT is regulated by transcription factors, such as Snail, ZEB, and Twist, and by signaling pathways including TGF-β, Wnt/β-catenin, and Notch, enabling cancer cells to adopt hybrid epithelial-mesenchymal states that confer phenotypic plasticity and drug tolerance. CAFs, derived from multiple cellular sources, further reinforce EMT programs through paracrine signaling, extracellular matrix remodeling, and metabolic reprogramming. This review critically synthesizes current evidence on EMT-CAF crosstalk in oncogenesis and therapeutic resistance, highlighting emerging clinical strategies, translational challenges, and lessons from failed or limited therapeutic approaches. By emphasizing EMT plasticity and CAF heterogeneity as convergent drivers of tumor adaptability, this work provides a refined framework for developing rational combination therapies targeting both cancer cells and their supportive stroma.

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor, has demonstrated efficacy in pivotal trials in both pretreated and treatment-naïve patients with ALK-positive non-small-cell lung cancer (NSCLC). However, real-world evidence from large multicenter cohorts remains limited.

Methods: We conducted a retrospective multicenter study including 114 patients with advanced ALK-positive NSCLC treated with brigatinib across 28 centers in Turkey between May 2020 and December 2024. Objective response rate (ORR) was assessed by RECIST v1.1. Median progression-free survival (mPFS) and overall survival (mOS) were estimated by the Kaplan-Meier method, and prognostic factors were analyzed using Cox regression.

Results: The median age was 55 years. Brigatinib was administered as first-line therapy in 68.4% of cases. In the overall cohort, the mPFS and OS were 24.2 and 44.2 months. The ORR was 70.2%. In the first-line setting, the ORR was 79.5%, with an mPFS of 28.6 months and an mOS of 50.3 months. In contrast, those treated in the second-line or later setting had less-favorable outcomes, which independently correlated with worse OS in multivariate analysis. Patients with baseline brain metastases achieved favorable outcomes, with an mPFS of 26.2 months, an mOS of 46.3 months, and an ORR of 76.5%. Adverse events were reported in 83.3% of patients, most commonly gastrointestinal toxicities, creatine phosphokinase elevation, and liver enzyme abnormalities.

Conclusion: This nationwide multicenter study offers comprehensive real-world evidence confirming the effectiveness and tolerability of brigatinib in ALK-positive NSCLC, with especially favorable outcomes in the first-line setting and in patients with brain metastases.

Introduction and objectives: Cryotherapy (CT) is increasingly used as a primary treatment for prostate cancer (PC), though guideline recommendations remain limited. This study evaluates toxicity, including the use of hypofractionation, as well as local and biochemical control, and survival outcomes in patients treated with salvage radiotherapy (sRT) after recurrence following CT.

Material and methods: We retrospectively analyzed 21 patients with recurrent PC after CT treated with sRT at our institution between 2013 and 2023. Toxicity was assessed with the RTOG scale, fractionation-related toxicity was compared with chi-square test. Biochemical recurrence was defined using Phoenix criteria. Survival and local control were analyzed with Kaplan-Meier method.

Results: Median follow-up was 56 months (4.4-136.6). Median age at diagnosis was 73 years (55-80), and median interval from CT to sRT was 45.5 months (14.2-189.23). Median radiation dose was 73.14 Gy (70-78); 86% received hormonal therapy, and 52% underwent hypofractionation. Acute grade 2 genitourinary (GU) toxicity occurred in 23.8%. Chronic GU grade 2 and 3 toxicities were 28.6% and 9.5%, respectively. Gastrointestinal (GI) toxicity included one case (4.76%) of acute G2 and one case each of chronic G3 and G4. No difference between conventional fractionation and hypofractionation was found. Median overall survival (OS) after sRT was 108.45 months (22.44-194.46). Mean OS was 98 months with 90.4% local control.

Conclusion: sRT after CT can provide durable local and biochemical control in selected patients, but severe late toxicity may occur in a small proportion of cases. Hypofractionation was not associated with increased toxicity in this cohort and appears to be a feasible option.

Background: Due to the challenges of identifying patients with hereditary cancer predispositions in oncology practice, we propose a comprehensive and practical tool intended for oncologists managing adult patients with malignant solid tumors and/or gastrointestinal polyps.

Methods: This tool was developed based on a comprehensive review of international guidelines, GeneReviews, and recent literature. Key criteria for genetic referral were compiled and organized by organ site and tumor subtype.

Results: The resulting resource includes a primary reference table for genetic referral, a polyposis-specific table, two visual summary figures and curated lists of associated genes and syndromes to streamline the clinical decision-making process.

Conclusions: This comprehensive tool aims to support oncologists in the timely identification of patients eligible for genetic counseling, thereby enhancing therapeutic decisions and improving familial risk assessment.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide, with 5-year survival rates below 21% primarily due to therapeutic resistance and metastatic progression. Genomic alterations in KRAS, EGFR, TP53, and MYC drive metabolic reprogramming that sustains tumor proliferation and therapy resistance. This review synthesizes evidence linking specific genomic alterations, including variant-specific KRAS alleles (G12C, G12D, and G12V) and TP53 gain- or loss-of-function mutations, to distinct metabolic phenotypes in NSCLC. It further examines the immunometabolic consequences of co-occurring mutations such as KRAS with TP53 or STK11/LKB1. The literature synthesis integrates genomic, metabolic, and immunologic profiling data to identify mutation-specific metabolic vulnerabilities and therapeutic targets. Genomic alterations establish distinct metabolic dependencies: KRAS-driven tumors exhibit enhanced glycolysis and glutaminolysis, EGFR-mutant tumors demonstrate increased lipogenesis, and TP53 loss promotes metabolic flexibility. Accumulation of lactate and depletion of glucose in the tumor microenvironment suppress CD8+ T-cell function, facilitating immune evasion. Rational combination strategies that pair genomic-targeted agents (sotorasib and adagrasib) with metabolic inhibitors (CB-839 and TVB-2640) show promise in overcoming adaptive resistance. Integrating genomic and metabolic profiling may enhance precision oncology approaches and improve clinical outcomes.

Purpose: We aimed to describe treatment patterns of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) who progressed after receiving darolutamide in a real-world setting, and according to the standard clinical practice in Spain.

Methods: This was a multicenter, observational, retrospective study conducted at the urology and oncology departments of 17 Spanish hospitals that participated in the ARAMIS trial and its rollover study.

Results: 85 patients, with a median age of 76 years, were included in the study. 49 patients (57.6%) progressed to mCRPC, with metastases located mainly in bone. Only 35 of them (71.4%) received at least one subsequent therapy. The most common first-line treatments after darolutamide were abiraterone (n = 22, 63%) and docetaxel (n = 10, 29%), with a median (IQR) treatment duration of 7.6 months (4.7, 12.7) and 4.8 months (3.8, 5.8), respectively; besides, the most frequent first-line/second-line treatment sequences were abiraterone-docetaxel and docetaxel-cabazitaxel. In addition, only 20% of patients with bone metastases received osteoclast-targeted therapy.

Conclusion: These real-world practice patterns suggest a lack of consensus in Spanish clinical practice for the management of patients with mCRPC, indicating that there is a need for more standardized strategies and unification of the criteria to make decisions in accordance with the recommendations of international clinical practice guidelines.

Clinical trial registration: Not applicable.

Background: Interleukin-17 (IL-17) plays a crucial role in the development of uterine corpus endometrial carcinoma (UCEC), but its prognostic and therapeutic implications remain unclear. This study aimed to investigate IL-17-related gene signatures and their potential as prognostic markers and therapeutic targets in UCEC.

Results: We developed a prognostic model based on four IL-17-related genes (SCGB1D2, SST, SELENOP, TMTC1) that predicted overall survival in UCEC. High-risk scores were associated with poorer survival outcomes and an immunosuppressive tumor microenvironment. In contrast, low-risk scores correlated with immune checkpoint upregulation and higher sensitivity to immune checkpoint blockade (ICB). Immunohistochemistry confirmed the upregulation of SCGB1D2 in UCEC tissues.

Conclusion: This IL-17-based prognostic model offers new insights into UCEC risk stratification and potential immunotherapeutic strategies. It highlights the clinical relevance of IL-17 signaling in personalized treatment approaches.

Anal cancer is rare but increasingly common, currently accounting for 2% of all digestive neoplasms. Some 50% of anal cancers are diagnosed at the localized stage, 29% as locoregional disease, and 12% as metastatic disease. When clinical suspicion of anal cancer exists, histological confirmation, correct local staging with MRI and distant staging with thoraco-abdominal CT, and management by a multidisciplinary team are mandatory. Chemoradiotherapy with 5-FU and mitomycin C (MMC) is the standard of care for early and locally advanced disease, while combination chemotherapy with a platinum-containing compound and taxanes is the treatment of choice for metastatic disease.