Doctoral Program in Cancer Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
Nat Rev Cancer. 2021 Aug;21(8):510-525. doi: 10.1038/s41568-021-00375-9. Epub 2021 Jul 9.
Oncogenic mutations in KRAS drive common metabolic programmes that facilitate tumour survival, growth and immune evasion in colorectal carcinoma, non-small-cell lung cancer and pancreatic ductal adenocarcinoma. However, the impacts of mutant KRAS signalling on malignant cell programmes and tumour properties are also dictated by tumour suppressor losses and physiological features specific to the cell and tissue of origin. Here we review convergent and disparate metabolic networks regulated by oncogenic mutant KRAS in colon, lung and pancreas tumours, with an emphasis on co-occurring mutations and the role of the tumour microenvironment. Furthermore, we explore how these networks can be exploited for therapeutic gain.
KRAS 致癌突变驱动常见的代谢程序，促进结直肠癌、非小细胞肺癌和胰腺导管腺癌中的肿瘤存活、生长和免疫逃逸。然而，突变 KRAS 信号对恶性细胞程序和肿瘤特性的影响也受到肿瘤抑制基因丢失和起源细胞和组织特有的生理特征的影响。在这里，我们综述了致癌性突变 KRAS 在结肠、肺和胰腺肿瘤中调节的趋同和不同的代谢网络，重点讨论了同时发生的突变和肿瘤微环境的作用。此外，我们还探讨了如何利用这些网络获得治疗收益。
