: Lung cancer remains the leading cause of cancer-related deaths worldwide. However, significant progress has been made individualizing therapy based on molecular aberrations (e.g., EGFR, ALK) and pathologic subtype. KRAS is one of the most frequently mutated genes in non-small cell lung cancer (NSCLC), found in approximately 30% of lung adenocarcinomas, and is thus an appealing target for new therapies. Although no targeted therapy has yet been approved for the treatment of KRAS-mutant NSCLC, there are multiple potential therapeutic approaches. These may include direct inhibition of KRAS protein, inhibition of KRAS regulators, alteration of KRAS membrane localization, and inhibition of effector molecules downstream of mutant KRAS. This article provides an overview of the KRAS pathway in lung cancer and related therapeutic strategies under investigation.
Implications for practice: The identification of oncogene-addicted cancers and specific inhibitors has revolutionized non-small cell lung cancer (NSCLC) treatment and outcomes. One of the most commonly mutated genes in adenocarcinoma is KRAS, found in approximately 30% of lung adenocarcinomas, and thus it is an appealing target for new therapies. This review provides an overview of the KRAS pathway and related targeted therapies under investigation in NSCLC. Some of these agents may play a key role in KRAS-mutant NSCLC treatment in the future.
摘要
肺癌仍然是全球癌症相关性死亡的首要原因。然而, 基于分子畸变 (如EGFR、ALK) 和病理亚型的个体化治疗已取得长足进展。KRAS是非小细胞肺癌 (NSCLC) 最常见的突变基因, 约可见于30%的肺腺癌, 因此可成为新疗法的靶点。尽管尚无治疗KRAS突变NSCLC的靶向疗法获得批准, 但已有多个潜在的疗法。这些疗法中, 可能包括直接抑制KRAS蛋白、抑制KRAS调节器、改变KRAS膜定位, 以及抑制突变KRAS下游效应器分子。本文对肺癌KRAS通路及在研的相关治疗策略进行了回顾。The Oncologist 2016;21:1450–1460
对临床实践的提示: 癌基因成瘾癌症及特异性抑制剂的发现为非小细胞肺癌 (NSCLC) 的治疗和转归带来了革命。KRAS是腺癌最常见的突变基因之一, 约可见于30%的肺腺癌患者, 因此也带来了新的治疗靶点。本综述回顾了KRAS通路以及在NSCLC中开展研究的相关靶向治疗。部分制剂可能在未来KRAS突变NSCLC的治疗中发挥重要作用。
Keywords: KRAS; MEK; Non-small cell lung cancer; Pathway; Selumetinib; Target; Trametinib.
©AlphaMed Press.