Abidoye Oluseyi, Hoyek Celine, Bekaii-Saab Tanios
Department of Hematology and Oncology, Mayo Clinic, Arizona.
Clin Adv Hematol Oncol. 2025 Mar-Apr;23(2):111-122.
Kirsten rat sarcoma virus (KRAS) is one of the prevalent oncogenic drivers in gastrointestinal (GI) cancers, including pancreatic ductal adenocarcinoma and colorectal cancer. The KRAS protein is a GTPase that activates several signaling pathways involved in cancer survival. Although KRAS mutations have long been considered difficult to target, recent advances have led to the development of small-molecule inhibitors targeting the mutations, particularly KRAS G12C. These inhibitors are showing promise in GI cancers. This review explores the molecular biology of KRAS mutations, their prevalence in GI malignancies, the current therapeutic approaches targeting KRAS, ongoing clinical trials, the challenges associated with resistance, and future directions for KRAS-targeted therapies in GI cancers.
Kirsten大鼠肉瘤病毒（KRAS）是胃肠道（GI）癌症中常见的致癌驱动因素之一，包括胰腺导管腺癌和结直肠癌。KRAS蛋白是一种GTP酶，可激活参与癌症存活的多种信号通路。尽管长期以来KRAS突变一直被认为难以靶向，但最近的进展已导致开发出针对这些突变的小分子抑制剂，特别是KRAS G12C。这些抑制剂在胃肠道癌症中显示出前景。本文综述探讨了KRAS突变的分子生物学、它们在胃肠道恶性肿瘤中的发生率、目前针对KRAS的治疗方法、正在进行的临床试验、与耐药相关的挑战以及胃肠道癌症中KRAS靶向治疗的未来方向。
