Dana-Farber Cancer Institute, Department of Medical Oncology, 450 Brookline Avenue, Boston, MA, USA.
Department of Biomedical Engineering and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Cell. 2021 Mar 4;184(5):1142-1155. doi: 10.1016/j.cell.2021.02.020.
The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy for most patients. Approaches to understand the function and circuitry of cancer genes provide complementary approaches to elucidate both oncogene and non-oncogene dependencies. Emerging work indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes. Here we describe a framework for this expanded list of cancer targets, providing novel opportunities for clinical translation.
癌症基因组的特征分析为肿瘤中体细胞改变的基因提供了深入了解，改变了我们对癌症生物学的认识，并使治疗策略得以定制。然而，大多数癌症等位基因的功能仍然是神秘的，许多癌症特征超越了它们的基因组。因此，肿瘤基因组特征分析并不能影响大多数患者的治疗。了解癌症基因的功能和电路的方法提供了互补的方法，以阐明致癌基因和非致癌基因的依赖性。新出现的工作表明，由非致癌基因依赖性产生的治疗靶点的多样性比反复突变基因的列表大得多。在这里，我们描述了这个扩展的癌症靶点列表的框架，为临床转化提供了新的机会。
