Boston University School of Medicine, Boston, MA, USA.
University of California, San Francisco, CA, USA.
Am Fam Physician. 2021 Feb 1;103(3):155-163.
Targeted cancer therapies involve chemotherapeutic agents that attack, directly or indirectly, a specific genetic biomarker found in a given cancer. Targeted oncology includes monoclonal antibodies, small molecule inhibitors, antibody-drug conjugates, and immunotherapy. For example, the monoclonal antibodies trastuzumab and pertuzumab target human epidermal growth factor receptor 2 (HER2) and are used when treating HER2-positive breast cancer. Although targeted oncology has improved survival by years for some incurable cancers such as metastatic breast and lung cancer, as few as 8% of patients with advanced cancer qualify for targeted oncology medications, and even fewer benefit. Other limitations include serious adverse events, illustrated by a 20% to 30% rate of heart attack, stroke, or peripheral vascular events among patients taking ponatinib, which is used in treating chronic myelogenous leukemia. Immune checkpoint inhibitor therapy-related adverse effects such as hypothyroidism are common, and more severe adverse events such as colitis and pneumonitis can be fatal and require immediate intervention. Drug interactions with widely prescribed medications such as antacids and warfarin are common. Additionally, financial toxicities are a problem for patients with cancer who are using costly targeted therapies. Future directions for targeted oncology include tumor-agnostic drugs, which target a given mutation and could be used in treating cancers from multiple organ types. An overview of indications, mechanism of action, and toxicities of targeted cancer therapies is offered here.
靶向癌症疗法涉及化疗药物,这些药物直接或间接地攻击特定癌症中发现的特定遗传生物标志物。靶向肿瘤学包括单克隆抗体、小分子抑制剂、抗体-药物偶联物和免疫疗法。例如,曲妥珠单抗和帕妥珠单抗是针对人表皮生长因子受体 2(HER2)的单克隆抗体,用于治疗 HER2 阳性乳腺癌。尽管靶向肿瘤学通过多年的治疗使一些无法治愈的癌症(如转移性乳腺癌和肺癌)的生存率得到了提高,但只有少数晚期癌症患者有资格使用靶向肿瘤学药物,而且受益的患者更少。其他限制包括严重的不良反应,例如接受 ponatinib 治疗的患者中有 20%至 30%的心脏病发作、中风或外周血管事件;ponatinib 用于治疗慢性髓性白血病。免疫检查点抑制剂治疗相关的不良反应,如甲状腺功能减退症很常见,更严重的不良反应,如结肠炎和肺炎,可能是致命的,需要立即干预。与广泛使用的药物(如抗酸剂和华法林)的药物相互作用很常见。此外,癌症患者使用昂贵的靶向治疗会产生财务毒性。靶向肿瘤学的未来发展方向包括肿瘤不可知论药物,这些药物针对特定的突变,可以用于治疗多种器官类型的癌症。本文概述了靶向癌症疗法的适应证、作用机制和毒性。