Koch Institute for Integrative Cancer Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Dana-Farber Cancer Institute, Boston, MA, USA.
Science. 2018 Jun 1;360(6392):962-963. doi: 10.1126/science.aar5986.
Understanding the molecular basis of cancer has led to a revolution in how cancers are classified and treated. Subsets of patients with specific genetic lesions are benefiting from precision medicine approaches utilizing the explosion of new drugs that target growth-promoting signaling networks. Unfortunately, relatively few cancer patients benefit from these approaches to target driver oncogenes [1]. Precision medicine is largely built on the assumption that cancer cell-intrinsic factors, such as genetic mutations or epigenetic identity, are the dominant determinants of which pathways and processes are required in cells and therefore determine response to therapies. However, in many cases, the presence of particular genetic lesions is insufficient to identify patients that will respond to a drug [1]. For instance, standard cell culture models have not been able to identify the subsets of cancer patients that respond to most conventional chemotherapies [1]. Nevertheless, these chemotherapy drugs remain standard of care for many cancers and in some cases contribute to curative regimens. Emerging data suggests that beyond cell-intrinsic factors, nutrient availability in the tumor microenvironment can also influence response to drugs. These results highlight the importance of understanding the microenvironmental factors that dictate which cellular processes are essential for disease progression and ultimately how tumors respond to treatments targeting these processes.
了解癌症的分子基础导致了癌症分类和治疗方法的革命性变化。具有特定遗传病变的患者亚组正在受益于利用新的靶向促进生长信号网络的药物的爆炸式增长的精准医学方法。不幸的是，相对较少的癌症患者受益于这些针对驱动致癌基因的方法[1]。精准医学在很大程度上基于这样一种假设，即癌细胞内在因素，如基因突变或表观遗传特征，是决定哪些途径和过程在细胞中是必需的，从而决定对治疗的反应的主要决定因素。然而，在许多情况下，特定遗传病变的存在不足以确定将对药物有反应的患者[1]。例如，标准的细胞培养模型还不能确定对大多数常规化疗有反应的癌症患者亚组[1]。然而，这些化疗药物仍然是许多癌症的标准治疗方法，在某些情况下有助于治愈方案。新出现的数据表明，除了细胞内在因素外，肿瘤微环境中的营养物质可用性也会影响对药物的反应。这些结果强调了了解决定疾病进展的细胞过程所必需的微环境因素以及肿瘤如何对针对这些过程的治疗做出反应的重要性。
