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Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer

Tue, 01 Dec 2026 00:00:00 GMT

Title: Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer Authors: Chen, Zhe; Qiang, Min; Dong, Junxue; Gong, Kejian; Zhang, Xinjun; Huo, Peng; Zhu, Jingjun; Shao, Yifeng; Ma, Jianzun; Zhang, Bowei; Liu, Wei; Tang, Mingbo Abstract: IntroductionSmall cell lung cancer (SCLC) initially responds well to cisplatin-based chemotherapy, but rapid development of drug resistance limits long-term efficacy and subsequent treatment options. Understanding the multifactorial mechanisms of cisplatin resistance is essential for improving patient outcomes. This review synthesizes recent preclinical and clinical advances, focusing on seven key resistance mechanisms and emerging therapeutic strategies, including immunotherapy, targeted therapy, and novel chemotherapeutic agents.DiscussionCisplatin resistance in SCLC arises through multiple mechanisms. First, reduction of drug deposition due to altered uptake or enhanced efflux decreases intracellular cisplatin levels. Second, dysregulation of apoptotic pathways, including overexpression of anti-apoptotic proteins such as Bcl-2, allows tumor cells to evade chemotherapy-induced cell death. Third, enhanced DNA damage repair restores cisplatin-induced lesions, limiting cytotoxicity. Fourth, the tumor microenvironment can induce resistance through stromal and immune interactions. Fifth, metabolic adaptations enable tumor cells to survive under chemotherapeutic stress. Sixth, SCLC subtype transitions alter cellular phenotype and chemosensitivity. Seventh, epigenetic changes drive transcriptional programs that confer resistance.Targeted therapies, such as multidrug resistance (MDR) inhibitors and Bcl-2 family inhibitors, can restore tumor sensitivity but are limited by toxicity and tumor-specific efficacy. Immunotherapy, including PD-1/PD-L1 and CTLA-4 inhibitors, shows potential, although effectiveness is constrained by the immunosuppressive tumor microenvironment and rapid progression. Targeted therapies, such as PARP inhibitors, demonstrate variable efficacy influenced by genetic heterogeneity, biomarker expression, and microenvironmental factors. Novel chemotherapeutic agents offer alternative options for cisplatin-resistant patients. Preclinical and early clinical studies suggest that combining these approaches may further enhance antitumor activity, potentially improving progression-free survival and quality of life. Biomarker-guided strategies may optimize personalized therapy and patient selection.DiscussionCisplatin resistance in SCLC arises through multiple mechanisms. First, reduction of drug deposition due to altered uptake or enhanced efflux decreases intracellular cisplatin levels. Second, dysregulation of apoptotic pathways, including overexpression of anti-apoptotic proteins such as Bcl-2, allows tumor cells to evade chemotherapy-induced cell death. Third, enhanced DNA damage repair restores cisplatin-induced lesions, limiting cytotoxicity. Fourth, the tumor microenvironment can induce resistance through stromal and immune interactions. Fifth, metabolic adaptations enable tumor cells to survive under chemotherapeutic stress. Sixth, SCLC subtype transitions alter cellular phenotype and chemosensitivity. Seventh, epigenetic changes drive transcriptional programs that confer resistance.Targeted therapies, such as multidrug resistance (MDR) inhibitors and Bcl-2 family inhibitors, can restore tumor sensitivity but are limited by toxicity and tumor-specific efficacy. Immunotherapy, including PD-1/PD-L1 and CTLA-4 inhibitors, shows potential, although effectiveness is constrained by the immunosuppressive tumor microenvironment and rapid progression. Targeted therapies, such as PARP inhibitors, demonstrate variable efficacy influenced by genetic heterogeneity, biomarker expression, and microenvironmental factors. Novel chemotherapeutic agents offer alternative options for cisplatin-resistant patients. Preclinical and early clinical studies suggest that combining these approaches may further enhance antitumor activity, potentially improving progression-free survival and quality of life. Biomarker-guided strategies may optimize personalized therapy and patient selection.ConclusionCisplatin resistance in SCLC is a complex, multifactorial process involving cellular, molecular, and microenvironmental mechanisms. Integrating mechanistic insights with emerging therapies, including immunotherapy, targeted therapy, and novel chemotherapeutics, offers a promising path to overcome resistance, guiding future research and the development of more effective, personalized treatment strategies for patients with cisplatin-resistant SCLC.

Clinical impact of local consolidative therapy in EGFR-mutant metastatic NSCLC: A propensity-matched multicenter analysis

Wed, 01 Jul 2026 00:00:00 GMT

Title: Clinical impact of local consolidative therapy in EGFR-mutant metastatic NSCLC: A propensity-matched multicenter analysis Authors: Lee, Eun Hye; Kim, Mi-Hyun; Kang, Da Hyun; Moon, Jisu; Kwak, Se Hyun; Eom, Jung Seop; Lee, Jeong Eun; Kim, Chi Young; Chang, Yoon Soo; Lee, Sang Hoon; Kim, Eun Young; Lee, Chang Young; Cho, Jaeho; 문지수 Abstract: Objectives To evaluate the impact of consolidative surgery and radiotherapy (RT) on survival outcomes in patients with advanced or metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). Methods This retrospective, multicenter cohort study included 864 patients with EGFR-mutant advanced or metastatic NSCLC receiving first-line EGFR-TKIs. Patients were categorized into EGFR-TKI monotherapy (n = 616), TKI plus surgery (n = 100), and TKI plus RT (n = 148). Propensity score matching (PSM) and overlap weighting were applied to balance baseline characteristics. Overall survival (OS) and progression-free survival (PFS) were analyzed using Cox proportional hazards models and restricted mean survival time (RMST). Results After PSM, 97 matched pairs were generated for TKI versus TKI plus surgery and 148 pairs for TKI versus TKI plus RT. Compared with TKI alone, consolidative surgery significantly improved OS (hazard ratio [HR], 0.36; 95% CI, 0.20-0.65; p < 0.001) and PFS (HR, 0.48; 95% CI, 0.34-0.67; p < 0.001), with RMST gains of 10.7 and 10.6 months.Consolidative RT showed a trend toward longer OS (HR, 0.61; 95% CI, 0.39-0.93; p = 0.023)without significant PFS or consistent RMST benefit. Subgroup analyses showed surgery benefit in younger patients with good performance, lower metastatic burden, and no brain metastasis, whereas RT effects were heterogeneous. Conclusion In this real-world cohort, consolidative surgery combined with EGFR-TKI was associated with a clear survival benefit in advanced EGFR-mutant NSCLC while the effect of consolidative RT was less consistent, highlighting the importance of careful patient selection and multidisciplinary management.

A large puncture closer of aortic wall by multi-memory actions with thrombo-hemodynamic control

Fri, 01 May 2026 00:00:00 GMT

Title: A large puncture closer of aortic wall by multi-memory actions with thrombo-hemodynamic control Authors: Cho, Sungwoo; Ha, Hyun-Su; Lee, Sangmin; Kim, Hyunjae; Lee, Seok Joon; Kim, Jueun; Lee, Yerin; Lee, Kang Suk; Joo, Hyun-Chel; Sung, Hak-Joon; 하현수; 이예린 Abstract: The vascular wall regulates the pattern and pressure of blood flow. In cardiovascular interventions, catheters are deployed by puncturing the vessel wall, without exception. Despite continuous progress, the outcomes remain highly operator-dependent, and large punctures with high-pressure bleeding continue to pose clinical challenges. As a translatable solution, this study introduces a shape memory vascular wall plug (VWP) that automates both the Body and Wing functions within a single component, supported by a Ring assembly to maximize pressure resistance. The VWP is deployed into a 6-mm puncture in a porcine thoracic aorta under peak blood pressure, and shape recovery is triggered by a 45 degrees C saline flush to enable automated activation. Upon recovery, Body expansion combined with Ring compression tightly seals the puncture tract. The curved Wing induces hemostatic sealing and then flattens to maintain healthy blood flow and physiologic pressures. The VWP achieves suturinglevel performance in aortic puncture closure, demonstrating effective hemostasis, patency, and endothelialization. The flow-blockage ratio required to balance hemostasis with hemodynamics is computationally modeled and validated using whole-blood microfluidics. Pressure resistance is maximized by tuning Ring strain through polymer blending, indicating multi-level strategies in polymer, device design, and memory function to advance the vascular closure technology.

GCC2 in Small Extracellular Vesicles as a Diagnostic and Prognostic Biomarker of Early-Stage Lung Adenocarcinoma

Fri, 01 May 2026 00:00:00 GMT

Title: GCC2 in Small Extracellular Vesicles as a Diagnostic and Prognostic Biomarker of Early-Stage Lung Adenocarcinoma Authors: Choi, Byeong Hyeon; An, Hyonggin; Cho, Sukki; Lee, Sungsoo; Kim, Hyeong Ryul; Cho, Jong Ho; Lee, Jun Hee; Kim, Ga Yoon; Jeon, Ok Hwa; Shin, Hyunku; Choi, Yeonho; Kim, Hyun Koo Abstract: Emerging evidence suggests that GRIP and coiled-coil domain-containing two enriched small extracellular vesicles (sEV-GCC2) may serve as diagnostic biomarkers of early-stage lung adenocarcinomas. However, the roles of these molecules remain unclear. This study evaluated the diagnostic and prognostic potential of sEV-GCC2 for detecting early-stage lung adenocarcinoma and its tumourigenic role in vitro and in vivo. This retrospective multicentre study analyzed 470 plasma samples (320 lung adenocarcinoma patients, 150 controls; mean follow-up: 34.7 +/- 24.0 months) across five institutions. Size-exclusion chromatography and enzyme-linked immunosorbent assay were used to measure sEV-GCC2 levels, whereas immunohistochemistry was used to confirm GCC2 expression in tumour tissues. Functional studies were performed using the PC9 and H1650 lung adenocarcinoma cell lines in vitro and the corresponding PC9-based preclinical models in vivo to evaluate the tumour-related effects of sEV-GCC2. Patients exhibited significantly elevated sEV-GCC2 levels compared to controls (area under the receiver operating characteristic (ROC) curve [AUC]: 0.904, P < 0.001), with similar results in stage TisN0-T1miN0 disease (AUC: 0.781, P < 0.001). sEV-GCC2 levels were associated with the pathological TNM stage and tumour location. Higher sEV-GCC2 levels were correlated with poorer recurrence-free survival (RFS), overall survival and recurrence rates, even in patients with stage 0-IA1 disease. Functional studies have revealed that sEV-GCC2, but not GCC2-deficient sEVs, promote cancer cell proliferation, tumour growth and lymph node metastasis in vitro and in vivo. These findings highlight the diagnostic and prognostic potential of sEV-GCC2 and its tumourigenic role in early-stage lung adenocarcinoma. This study was registered at ClinicalTrials.gov (NCT04529915)