University of California San Francisco, San Francisco, California.
Cancer. 2019 Dec 1;125(23):4139-4147. doi: 10.1002/cncr.32163. Epub 2019 Aug 21.
Despite recent advances in the management of colorectal cancer, metastatic disease remains challenging, and patients are rarely cured. However, a better understanding of the pathways implicated in the evolution and proliferation of cancer cells has led to the development of targeted therapies, that is, agents with action directed at these pathways/features. This approach is more specific to cells within which these pathways, such as epidermal growth factor receptor (EGFR), are overactive; this is in contrast to the relatively indiscriminate mechanism by which cytotoxic chemotherapy tends to affect rapidly dividing cells, regardless of their role. Although factors unique to a given patient, such as the location of the primary tumor (sidedness) or the presence of mutations that confer resistance, may limit the utility of these agents, targeted therapies are now a part of the treatment paradigm for metastatic colorectal cancer, and survival outcomes have significantly improved. This review provides an overview of the role of targeted therapy in the management of patients with colorectal cancer metastases as well as a discussion of issues in patient selection, with a focus on inhibitors of angiogenesis, EGFR-targeted therapy, BRAF mutation-targeted therapies, and other novel strategies, including immunotherapy.
尽管结直肠癌的治疗近年来取得了进展,但转移性疾病仍然具有挑战性,患者很少被治愈。然而,对参与癌细胞进化和增殖的途径的更好理解导致了靶向治疗的发展,即针对这些途径/特征的药物。这种方法针对这些途径过度活跃的细胞更为特异,例如表皮生长因子受体(EGFR);这与细胞毒性化疗倾向于影响快速分裂细胞的相对无差别机制形成对比,而不论其作用如何。尽管特定患者的因素(例如原发性肿瘤的位置(侧别)或赋予耐药性的突变的存在)可能限制这些药物的效用,但靶向治疗现在是转移性结直肠癌治疗范例的一部分,并且生存结果已显著改善。本综述提供了靶向治疗在管理结直肠癌转移患者中的作用概述,以及对患者选择问题的讨论,重点是血管生成抑制剂、EGFR 靶向治疗、BRAF 突变靶向治疗和其他新策略,包括免疫疗法。