Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
Expert Opin Investig Drugs. 2020 Apr;29(4):399-409. doi: 10.1080/13543784.2020.1740680. Epub 2020 Mar 19.
: Focal adhesion kinase (FAK) is a promising target for the treatment of solid tumors because its expression has been linked to tumor progression, invasion, and drug resistance. Several FAK inhibitors have been developed and tested for efficacy in treating advanced cancers. Four FAK inhibitors have shown promising preclinical data and have advanced to clinical development in solid tumors.: This article provides a systematic review on FAK inhibitors that have been tested or are currently in clinical trials in advanced solid tumors. We discuss the efficacy of GSK2256098, PF-00562271, VS-6063, and BI 853520 in the preclinical setting and summarize the results of phase I/II clinical trials evaluating these compounds.: The FAK inhibitors examined in clinical trials thus far have been shown to have manageable toxicity profiles and have demonstrated cytostatic effects as single agents, extending progression-free survival without producing a clinical or radiographic response. Trials are currently underway to strengthen the efficacy of treatment by combining FAK inhibitors with cytotoxic chemotherapy, targeted therapy, or immunotherapy. In the future, prognostic markers must be identified to carefully select patients who could benefit from FAK inhibitor treatment alone or in combination strategies.
: 黏着斑激酶（FAK）是治疗实体瘤的一个有前途的靶点，因为它的表达与肿瘤的进展、侵袭和耐药性有关。已经开发了几种 FAK 抑制剂，并对其在治疗晚期癌症方面的疗效进行了测试。有 4 种 FAK 抑制剂已显示出有希望的临床前数据，并在实体瘤的临床开发中取得进展。: 本文对已在晚期实体瘤中进行测试或正在进行临床试验的 FAK 抑制剂进行了系统评价。我们讨论了 GSK2256098、PF-00562271、VS-6063 和 BI 853520 在临床前研究中的疗效，并总结了评估这些化合物的 I/II 期临床试验的结果。: 迄今为止，在临床试验中检查的 FAK 抑制剂显示出可管理的毒性特征，并作为单一药物表现出细胞抑制作用，延长无进展生存期，而没有产生临床或影像学反应。目前正在进行临床试验，以通过将 FAK 抑制剂与细胞毒性化疗、靶向治疗或免疫疗法相结合来增强治疗效果。未来，必须确定预后标志物，以仔细选择可能受益于 FAK 抑制剂单独治疗或联合治疗策略的患者。
