Shi Yanyan, Zheng Huiling, Wang Tianzhen, Zhou Shengpu, Zhao Shiqing, Li Mo, Cao Baoshan
Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, China.
Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, China.
Mol Cancer. 2025 Jan 11;24(1):9. doi: 10.1186/s12943-024-02216-3.
The Kirsten rat sarcoma viral oncogene homolog (KRAS) protein plays a key pathogenic role in oncogenesis, cancer progression, and metastasis. Numerous studies have explored the role of metabolic alterations in KRAS-driven cancers, providing a scientific rationale for targeting metabolism in cancer treatment. The development of KRAS-specific inhibitors has also garnered considerable attention, partly due to the challenge of acquired treatment resistance. Here, we review the metabolic reprogramming of glucose, glutamine, and lipids regulated by oncogenic KRAS, with an emphasis on recent insights into the relationship between changes in metabolic mechanisms driven by KRAS mutant and related advances in targeted therapy. We also focus on advances in KRAS inhibitor discovery and related treatment strategies in colorectal, pancreatic, and non-small cell lung cancer, including current clinical trials. Therefore, this review provides an overview of the current understanding of metabolic mechanisms associated with KRAS mutation and related therapeutic strategies, aiming to facilitate the understanding of current challenges in KRAS-driven cancer and to support the investigation of therapeutic strategies.
Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）蛋白在肿瘤发生、癌症进展和转移中起关键的致病作用。众多研究已探讨了代谢改变在KRAS驱动的癌症中的作用，为在癌症治疗中靶向代谢提供了科学依据。KRAS特异性抑制剂的研发也引起了相当大的关注，部分原因是获得性治疗耐药性带来的挑战。在此，我们综述了致癌性KRAS调控的葡萄糖、谷氨酰胺和脂质的代谢重编程，重点阐述了对KRAS突变驱动的代谢机制变化与靶向治疗相关进展之间关系的最新见解。我们还关注了KRAS抑制剂在结直肠癌、胰腺癌和非小细胞肺癌中的发现进展及相关治疗策略，包括当前的临床试验。因此，本综述概述了目前对与KRAS突变相关的代谢机制及相关治疗策略的理解，旨在促进对KRAS驱动的癌症当前挑战的理解，并支持治疗策略的研究。
