kras突变肺癌的治疗机制及最新进展

Cynthia Hsin-Ya Chao, Yuanpu Peter Di
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引用次数: 0

摘要

肺癌是癌症相关死亡的主要原因,在所有癌症中死亡率最高。尽管近年来癌症治疗取得了重大进展,特别是随着检查点抑制剂免疫疗法的发展,但尚未发现治愈肺癌的确切治疗方法。肺肿瘤发生涉及一个多步骤的遗传改变过程,具有异质性和多样性,因此,尽管吸烟已被广泛认为是一个主要的相关危险因素,但许多非吸烟者仍会患上肺癌。在肺癌中,85% %是非小细胞肺癌(NSCLC),其中腺癌是最常见的NSCLC亚型,约占所有肺癌的40% %。主要的基因突变驱动因素包括表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)和Kirsten大鼠肉瘤病毒癌基因同源物(KRAS)。虽然新一代抗癌药物的进步已经成功治疗了EGFR-和alk -相关的肺癌,但KRAS突变相关的肺癌仍然极具挑战性,治疗选择有限。这篇综述概述了肺癌的病因、流行病学和分类,描述了目前的治疗选择和局限性,重点是治疗最具挑战性的kras突变肺癌。此外,本文通过描述各种进入临床试验的kras靶向治疗的机制和效用,重点介绍了kras突变癌症治疗的现状和发展,并强调了最有希望的治疗方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanisms and current advances in treating KRAS-mutated lung cancer
Lung cancer is the leading cause of cancer-related deaths, with the highest mortality among all cancers. Despite the significant advances in cancer treatments in recent years, especially with the development of checkpoint inhibitor immunotherapy, a definitive treatment has yet to be discovered to cure lung cancer. Lung tumorigenesis involves genetic alterations in a multi-step process with heterogeneity and diversity, such that even though cigarette smoke has been widely acknowledged as a major associated risk factor, many non-smokers still develop lung cancer. Among lung cancers, 85 % are non-small cell lung carcinoma (NSCLC), with adenocarcinoma as the most prevalent NSCLC subtype, making up around 40 % of all lung cancers. The major genetic mutation drivers include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS). While the advancement of newer-generation anti-cancer drugs has successfully treated EGFR- and ALK-associated lung cancers, KRAS mutation-associated lung cancer remains extremely challenging and has limited therapeutic options. This review outlines the etiology, epidemiology, and categorization of lung cancer, describing the current therapeutic options and limitations, with a focus on the most challenging-to-treat KRAS-mutated lung cancer. Furthermore, this paper highlights the current state and development of KRAS-mutated cancer treatment by describing the mechanisms and utilities of various KRAS-targeted therapies entering clinical trials, and it underlines the most promising treatment options.
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来源期刊
Chinese medical journal pulmonary and critical care medicine
Chinese medical journal pulmonary and critical care medicine Critical Care and Intensive Care Medicine, Infectious Diseases, Pulmonary and Respiratory Medicine
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