Dekker Simone E, Deng Lei
Division of Hematology and Oncology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Cancers (Basel). 2024 Nov 20;16(22):3885. doi: 10.3390/cancers16223885.
KRAS mutation is one of the most common oncogenic drivers in non-small cell lung cancer. Since its discovery about four decades ago, drug development targeting KRAS has been met with countless failures. Recently, KRAS G12C, a subvariant of KRAS, became the first druggable KRAS mutation. The efficacy of the first-generation KRAS inhibitor is modest, but with scientific advancement, KRAS G12C inhibitors with higher potency are on the horizon. Additionally, novel therapeutic approaches targeting other KRAS subvariants are also being explored in clinical trials with encouraging early data. We will review the clinical advances and challenges for patients with KRAS-mutated non-small cell lung cancer, with a focus on small molecule inhibitors.
KRAS突变是非小细胞肺癌中最常见的致癌驱动因素之一。自大约四十年前被发现以来，针对KRAS的药物研发遭遇了无数次失败。最近，KRAS的一个亚型KRAS G12C成为首个可靶向治疗的KRAS突变。第一代KRAS抑制剂的疗效一般，但随着科学的进步，更高效的KRAS G12C抑制剂即将问世。此外，针对其他KRAS亚型的新型治疗方法也正在临床试验中进行探索，早期数据令人鼓舞。我们将综述KRAS突变型非小细胞肺癌患者的临床进展和挑战，重点关注小分子抑制剂。
