Poor therapeutic outcomes in KRAS-mutant non-small cell lung cancer due to chemoresistance conferred by SLC7A11.

IF 2.8 3区医学 Q2 ONCOLOGY

Clinical & Translational Oncology Pub Date : 2025-02-01 Epub Date: 2024-07-26 DOI:10.1007/s12094-024-03592-4

Shiyu Zhang, Yutong Ge, Jingwen Liu, Kaihua Lu

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引用次数: 0

Abstract

Purpose: This study aimed to confirm whether Kirsten rat sarcoma viral oncogene (KRAS) mutations affect the therapeutic efficacy of non-small cell lung cancer (NSCLC) and, if so, to explore what the possible mechanisms might be.

Methods: We retrospectively analyzed the efficacy of immunochemotherapy in KRAS-mutant NSCLC patients compared to driver-negative patients. Online data platforms were used to find immunotherapy cases, and survival analysis compared treatments' efficacy. Cytotoxicity assays measured chemosensitivity in KRAS-mutant versus wild-type NSCLC to drugs like paclitaxel, carboplatin, and pemetrexed. Bioinformatics confirmed the KRAS-SLC7A11 link and cell experiments tested SLC7A11's role in chemoresistance. Animal studies verified the antitumor effects of SLC7A11 inhibitors with chemotherapy.

Results: Patients with KRAS-mutated NSCLC have a shorter therapeutic effectiveness duration with immunochemotherapy than patients with driver gene-negative status. The efficacy of immunotherapy alone is similar between the two groups. The KRAS mutation can enhance chemoresistance by upregulating SLC7A11, and inhibiting SLC7A11 can increase the sensitivity of KRAS-mutated NSCLC to chemotherapy.

Conclusion: This study suggests that KRAS-mutant NSCLC can enhance its acquired chemoresistance by overexpressing SLC7A11, leading to poorer therapeutic outcomes. Targeting the KRAS-SLC7A11 axis could increase sensitivity to chemotherapeutic drugs, providing theoretical support for future treatment directions.

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SLC7A11产生的化疗耐药性导致KRAS突变非小细胞肺癌治疗效果不佳。

目的：本研究旨在证实克氏大鼠肉瘤病毒癌基因（KRAS）突变是否会影响非小细胞肺癌（NSCLC）的疗效，如果会，则探讨可能的机制：我们回顾性地分析了KRAS突变NSCLC患者与驱动因素阴性患者相比免疫化疗的疗效。我们利用在线数据平台查找免疫治疗病例，并通过生存分析比较治疗效果。细胞毒性分析测定了KRAS突变型与野生型NSCLC患者对紫杉醇、卡铂和培美曲塞等药物的化疗敏感性。生物信息学证实了 KRAS-SLC7A11 的联系，细胞实验测试了 SLC7A11 在化疗抗药性中的作用。动物实验验证了 SLC7A11 抑制剂与化疗的抗肿瘤效果：结果：与驱动基因阴性的患者相比，KRAS突变的NSCLC患者接受免疫化疗的疗效持续时间较短。两组患者单独使用免疫疗法的疗效相似。KRAS突变可通过上调SLC7A11增强化疗耐药性，而抑制SLC7A11可增加KRAS突变NSCLC对化疗的敏感性：本研究表明，KRAS突变的NSCLC可通过过表达SLC7A11增强其获得性化疗耐药性，从而导致较差的治疗效果。针对KRAS-SLC7A11轴可提高化疗药物的敏感性，为未来的治疗方向提供理论支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical & Translational Oncology 医学-肿瘤学

CiteScore

6.20

自引率

2.90%

发文量

240

审稿时长

1 months

期刊介绍： Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.