Clinical & Translational Oncology最新文献

The evolution of cancer therapies has dramatically improved patient survival but has also revealed a critical challenge: the long-term genotoxic effects that can lead to secondary primary malignancies (SPMs). This review synthesizes current knowledge on how diverse treatment modalities, including chemotherapy, radiotherapy, targeted agents, and immunotherapies, induce DNA damage in normal tissues. It details the distinct mechanisms of genotoxicity, from the direct DNA lesions caused by cytotoxic drugs and ionizing radiation to the indirect damage mediated by oxidative stress and inflammation from newer therapies. The article identifies a range of multifactorial risk factors for SPMs, encompassing patient-specific variables such as age, genetic predisposition, and lifestyle, as well as therapy-related factors such as dose, duration, and combination regimens. It then evaluates the progression of monitoring methods, from traditional cytogenetic assays to advanced molecular and multi-omics biomarkers, highlighting their potential to predict individual susceptibility and inform risk stratification. By exploring pharmacogenomics and its role in genotype-guided dosing, the review proposes a framework for personalized prevention strategies. These strategies include risk-adapted regimens, prophylactic interventions, and the use of AI-driven predictive models. Ultimately, this comprehensive analysis underscores the urgent need to advance personalized prevention in oncology to balance therapeutic efficacy with long-term genomic safety for cancer survivors.

Ovarian cancer is a deadly gynecological malignancy, often detected late with frequent recurrence and treatment resistance. Non-coding RNAs, particularly long non-coding RNAs (lncRNAs), are now recognized as crucial regulators of cancer pathogenesis. This review synthesizes current literature to elucidate the molecular and functional roles of the lncRNA HAGLROS in ovarian cancer, focusing on its interactions within competing endogenous RNA (ceRNA) networks. HAGLROS, located at 2q31.1, is an oncogenic lncRNA that promotes ovarian cancer progression. It drives enhanced cell proliferation, metastasis, and chemotherapy resistance while inhibiting apoptosis. Its oncogenic activity is primarily mediated through intricate sponging interactions with microRNAs (miRNAs), disrupting post-transcriptional gene regulation and influencing epigenetic and transcriptional processes. The dysregulation of HAGLROS underscores its significant role in ovarian tumorigenesis. Its ability to modulate key cancer hallmarks via miRNA interactions reveals complex regulatory axes central to the disease's pathogenesis. HAGLROS represents a promising candidate for early diagnostic biomarkers and novel therapeutic interventions. Further investigation into the HAGLROS-miRNA-mRNA network is essential for defining its clinical utility and developing targeted treatments for ovarian cancer.

Purpose: To evaluate the disproportionality, time to onset, reporting frequency, and outcomes of hematologic AEs associated with trastuzumab deruxtecan (T-DXd) using data from the Japanese Adverse Drug Event Report database (JADER).

Methods: We analyzed data for the period from April 2004 to December 2024. Data on hematologic AEs were extracted, and the disproportionality of T-DXd-associated AEs was assessed by calculating reporting odds ratios.

Results: Among the 3,221,393 reports analyzed, 1561 were associated with T-DXd, including 433 hematologic AEs. Signals were detected for six AEs, including febrile neutropenia, anaemia, neutrophil count decreased, neutropenia, platelet count decreased, and myelosuppression. All had fatal cases, with particularly high fatality rates observed for febrile neutropenia and platelet count decreased. A histogram of median times to onset showed that febrile neutropenia and platelet count decreased typically occurred within 8 to 10.5 days after administration. Weibull distribution analysis indicated that febrile neutropenia showed an early-onset tendency (early failure type), whereas platelet count decreased occurred in a dose-dependent manner (wear-out failure type).

Conclusions: Some hematologic AEs associated with T-DXd can be fatal and may occur not only early in treatment but also later in the course. Continuous monitoring is essential for their timely detection and appropriate management.

Background: Cadonilimab is a novel PD-1/CTLA-4 bispecific antibody approved for cervical cancer treatment in China in 2022. We conducted a retrospective study to investigate the efficacy and safety of Cadonilimab in patients with recurrent or metastatic gynecological malignancies.

Methods: We retrospectively enrolled 27 patients with recurrent or metastatic gynecological malignancies, confirmed by pathology or cytology between July 2022 and February 2025. All patients received at least two cycles of Cadonilimab. The primary endpoints were objective response rate and disease control rate according to RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Results: In the enrolled population, the mPFS and mOS were 10.90 months (95% CI: 9.57-12.23) and 52.93 months (95% CI: 19.62-73.38), respectively. Among the first-line patients with advanced cervical cancer, ORR was 66.67% (10/15,95% CI, 41.71 to 84.82), DCR was 100.00% (15/15,95% CI 79.67 to 100.00), the mPFS and mOS were 15.9 months (95% CI: 7.72-24.08) and 46.5 months (95% CI: 19.62-73.38), respectively. There was no significant difference in PFS (P = 0.45, HR: 1.704, 95% CI: 0.38-7.70) and OS (P = 0.91, HR: 1.14, 95% CI: 0.11-11.46) between Cadonilimab-based chemotherapy with or without bevacizumab. In the responder population, 14 (51.85%) patients experienced at least one treatment-related adverse event (TRAE), only 1(3.70%) patient developed grade 3-4 adverse events. No treatment-related deaths occurred during the study.

Conclusion: Cadonilimab-based chemotherapy with or without bevacizumab had a promising efficacy and manageable safety profile in the treatment of recurrent or metastatic gynecological malignancies.

Background: Hepatocellular carcinoma (HCC) is treated with sorafenib as a first-line treatment; however, resistance reduces its clinical effectiveness. It has been demonstrated that CCDC137 influences cell survival and proliferation. However, in HCC, its role in sorafenib resistance has not been thoroughly investigated.

Objective: This study examined how CCDC137 makes HCC cells resistant to sorafenib, with a focus on the Akt/mTOR signaling pathway.

Methods: HCC cell lines resistant to sorafenib (Huh7/sora) were generated by gradually increasing sorafenib concentrations in Huh7 cells. Bioinformatics analysis was performed on the Cancer Genome Atlas (TCGA)-hepatocellular carcinoma (LIHC) dataset and the GSE29721 dataset. The prognostic significance of CCDC137 was verified using Kaplan-Meier survival curves. Using the in vitro cell assays, the consequences of CCDC137 for the migration, apoptosis, invasion, and proliferation of parental HCC cells and sorafenib-resistant cells were assessed. The changes were analyzed using the Western blot test in the AKT/mTOR signaling pathway in resistant cells after CCDC137 knockdown or overexpression.

Results: CCDC137 was significantly elevated in Huh7/sora cells resistant to sorafenib and was linked to a poor outcome for individuals with HCC. CCDC137 knockdown reduced cell viability, induced apoptosis and inhibited migration and invasion in Huh7/sora cells. Conversely, CCDC137 overexpression in Huh7 cells enhanced sorafenib resistance. Mechanistically, CCDC137 activated the Akt/mTOR signaling pathway, AKT inhibition with MK2206 reversed opposition and increased apoptosis in resistant cells.

Conclusion: Through triggering the Akt/mTOR signaling pathway, CCDC137 encourages sorafenib resistance in HCC cells, potentially offering a treatment approach to combat sorafenib resistance in HCC cells.

Despite advances in patients' healthcare, gastric cancer remains a major health concern around the world with a high annual incidence rate and mortality. This highlights the urgent need to develop more effective therapeutic strategies, particularly for patients in advanced stages of the disease. In the recent decade, cellular-based immunotherapy has achieved remarkable successes in various hematologic malignancies and solid tumors. Nonetheless, until now, no cellular-based immunotherapy has been approved for GC patients. This review aims to provide a holistic view of the current state of cellular-based immunotherapy for GC, its existing bottlenecks, and future directions to harness the potential of cellular-based immunotherapy for GC treatment. In this regard, we explore clinical trials of various types of cellular-based immunotherapy, including chimeric antigen receptor (CAR)-engineered cell therapy, T cell receptor (TCR)-engineered T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, cytokine-induced killer (CIK) cell therapy, and dendritic cell (DC) vaccines. For each type of cellular-based immunotherapy, we discuss existing roadblocks to successful treatment and explore potential solutions that may improve efficacy, including novel targets, combination approaches, and biomarker-driven patient selection.

Purpose: Giant thick melanomas (GTMs) are rare tumors characterized by extreme size and depth. We aimed to describe their clinical features and outcomes.

Methods/patients: We retrospectively reviewed eleven patients diagnosed with GTMs at a tertiary dermatology center. GTMs were defined as primary cutaneous melanomas with diameter > 5 cm and Breslow thickness > 4 mm. Tumor size was measured clinically, and all histopathology was reviewed by two dermatopathologists. Clinical, pathological, treatment, and outcome data were extracted from electronic records.

Results: Eleven patients (median age 69 years) presented with large tumors (median diameter 55 mm; median Breslow thickness 12 mm), most often on the trunk or extremities. Over half (54.5%) had stage III-IV disease at diagnosis, and treatments included surgery and systemic therapy. Median overall survival was 13 months, with two long-term survivors.

Conclusions: GTMs are aggressive and frequently diagnosed at advanced stages. Early recognition and multidisciplinary management are essential. Giant thick melanoma (GTM) is a rare entity characterized by aggressive behavior and poor prognosis. We conducted a retrospective descriptive study defining GTM as lesions with a diameter > 5 cm and Breslow thickness > 4 mm. Eleven cases were analyzed (mean age: 68.5 years), with a female predominance and predominant localization on the trunk. The main reasons for consultation were tumor growth, bleeding, and neurological symptoms. At diagnosis, AJCC stages ranged from IIB to IV. During follow-up, seven patients died -five due to melanoma and two from other causes-, while two remain alive and under active follow-up. Median follow-up was 1 year (range 0-15 years; mean 3.5 years). These findings confirm the severity of GTM and highlight the persistence of diagnostic delay. The main limitation of this study is the small sample size.

Purpose: Gastric cancer is a leading cause of cancer-related mortality worldwide, with metastasis being the primary cause of death. Exosomes secreted by tumor cells are key mediators of intercellular communication and can prepare distant sites for metastasis by altering the local microenvironment. We hypothesized that exosomes released by gastric cancer cells deliver cargo that regulates specific proteins in recipient gastric cancer cells, thereby enhancing tumor progression and metastatic potential.

Methods: Human gastric cancer cell lines were treated with exosomes isolated from the conditioned medium of other gastric cancer cells. Differential proteomic analysis was performed to identify proteins significantly altered by exosome treatment. ITGA2 expression was validated in exosome-treated cells and in clinical gastric cancer tissues versus adjacent normal tissues using RT-qPCR and western blotting. The functional role of ITGA2 was assessed by siRNA-mediated knockdown, followed by MTT proliferation assays and fluorometric transwell assays for migration and invasion. A second proteomic analysis was conducted on ITGA2-knockdown versus control cells to identify downstream targets and affected pathways.

Results: Exosome treatment significantly upregulated ITGA2 expression in recipient gastric cancer cells. ITGA2 was also markedly overexpressed in human gastric cancer tissues compared with adjacent normal mucosa. Knockdown of ITGA2 significantly suppressed cell proliferation, migration, and invasion. Proteomic profiling of ITGA2-knockdown cells revealed numerous differentially expressed proteins enriched in pathways related to cell adhesion, motility, extracellular matrix organization, and intercellular signaling.

Conclusion: Exosomes derived from gastric cancer cells induce ITGA2 overexpression in recipient tumor cells, where ITGA2 functions as an oncogene that promotes proliferation, migration, and invasion. The downstream targets of ITGA2 implicate multiple pro-tumorigenic signaling networks, suggesting that the exosomes-ITGA2 axis may represent a novel therapeutic target in gastric cancer progression and metastasis.

Background: Cancer patients often develop life-threatening events that prompt intensive care unit (ICU) admission. However, uncertainty regarding prognosis may hinder timely referral. We compared ICU survival in adults with solid tumors admitted emergently for medical or urgent surgical reasons with that of non-cancer controls.

Methods: We retrospectively analyzed 167 consecutive adults with solid tumors emergently admitted to a mixed ICU in a single center between 2010 and 2016, and compared them with two propensity-matched non-cancer cohorts. We made two 1:1 comparisons: (1) cancer and non-cancer patients matched for age, sex and do-not-intubate order; (2) the same cancer cohort matched additionally for admission diagnosis, maximum SOFA, SAPS II and Charlson Comorbidity Index. Primary outcome was ICU mortality; hospital mortality and 90-day survival were secondary endpoints.

Results: Cancer cases represented 4.8% of all ICU admissions; 54% had metastatic disease, 41% acute respiratory failure, and 28.7% sepsis/shock. When matched only for demographic and functional factors, cancer patients had higher intensive care unit and hospital mortality rates than controls (27.5% vs 10.8%, p < 0.001, and 35.3% vs 16.2%, p < 0.001, respectively). After matching for severity and comorbidity, ICU and hospital mortality no longer differed significantly (27.5% vs 19.8%; p = 0.094, and 35.3% vs 28.7%; p = 0.4). 90-day survival was significantly lower for cancer patients (64.7% vs 80.2%, p < 0.001), but no differences were found with controls matched for severity and comorbidity (64.7% vs 71.3%, p = 0.4).

Conclusions: Solid-tumor patients admitted to the ICU are generally more severely ill and thus present higher crude mortality than non-cancer patients. However, when severity and comorbidity are equivalent, outcomes are similar. Therefore, intensive care should be offered to cancer patients with reversible critical illness and acceptable baseline status, and a cancer diagnosis alone should not be considered a contraindication for ICU admission.

Background: The SEC13 is a multifaceted gene implicated in mTORC1 signaling regulation and the maintenance of genomic stability. Its function in cancer is complex, displaying potential oncogenic as well as potential tumor-suppressive roles across different malignancies. Therefore, this study aimed to investigate SEC13 expression, prognostic value, and its relationship with immune checkpoints across different cancer types.

Methods: Differential expression analysis, diagnostic analysis, and prognostic analysis were analyzed with The Cancer Genome Atlas and Human Protein Atlas database. The potential related genes were analyzed by utilizing Gene Expression Omnibus and clinical breast cancer samples. GO (Gene Ontology) and GSEA (Gene Set Enrichment Analysis) were used to elucidate the potential role of SEC13. TMB (tumor mutation burden), MSI (microsatellite instability), immune checkpoint, and immune cell infiltration were also analyzed to indicate its potential role in immune feature. To validate the functional impact of SEC13, its effects on cell proliferation and cell cycle distribution were assessed using CCK-8 assays and flow cytometry in MDA-MB-231 and MCF7 breast cancer cells following SEC13 knockdown.

Results: SEC13 was highly expressed in 14 tumor types and lowly expressed in 2 tumor types. High expression of SEC13 was associated with worse overall survival, disease-specific survival, and progression-free interval in breast cancer, liver hepatocellular carcinoma, and sarcoma. SEC13 expression was correlated with several co-expressed genes (e.g., MED8, RPN1) and was enriched in cell cycle pathway. Functionally, SEC13 knockdown was found to reduce the S-phase cell proportion and inhibit cell proliferation. In addition, SEC13 exhibited relationships with TMB and MSI, immune checkpoint, and immune cell infiltration.

Conclusion: This study underscores the significant expression differences and prognostic implications of SEC13 in various cancers, emphasizing its potential as a biomarker and therapeutic target.