Department of Pharmacology, Wayne State University School of Medicine, Michigan, MI, USA; Department of Oncology, Wayne State University School of Medicine and Tumor Biology and Microenvironment Research Program, Barbara Ann Karmanos Cancer Institute, Michigan, MI, USA.
Department of Molecular Biology, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research Princeton Branch, Princeton, NJ, USA.
Trends Cancer. 2023 Jan;9(1):69-82. doi: 10.1016/j.trecan.2022.08.007. Epub 2022 Sep 30.
Development of cancer therapeutics has traditionally focused on targeting driver oncogenes. Such an approach is limited by toxicity to normal tissues and treatment resistance. A class of 'cancer fitness genes' with crucial roles in metastasis have been identified. Elevated or altered activities of these genes do not directly cause cancer; instead, they relieve the stresses that tumor cells encounter and help them adapt to a changing microenvironment, thus facilitating tumor progression and metastasis. Importantly, as normal cells do not experience high levels of stress under physiological conditions, targeting cancer fitness genes is less likely to cause toxicity to noncancerous tissues. Here, we summarize the key features and function of cancer fitness genes and discuss their therapeutic potential.
癌症治疗药物的研发传统上一直聚焦于靶向驱动致癌基因。然而,这种方法受到正常组织毒性和治疗耐药性的限制。目前已经鉴定出一类在转移中具有关键作用的“癌症适应性基因”。这些基因的活性升高或改变并不会直接导致癌症,而是减轻肿瘤细胞所面临的压力,帮助它们适应不断变化的微环境,从而促进肿瘤的进展和转移。重要的是,由于正常细胞在生理条件下不会经历高水平的应激,因此靶向癌症适应性基因不太可能对非癌组织造成毒性。在这里,我们总结了癌症适应性基因的关键特征和功能,并讨论了它们的治疗潜力。