NSCLC 是全球癌症相关死亡的主要原因，其存活率较低主要是由于 NSCLC 经常产生化疗耐药性。粘着斑激酶 (FAK) 是一种非受体酪氨酸激酶，参与调节细胞内多个过程的途径，包括存活、迁移和 TME，这些过程有助于肿瘤进展和耐药性。最近，FAK 抑制剂 (FAKi) 在治疗 NSCLC 方面显示出巨大的潜力。这篇叙述性综述旨在总结涉及 FAK 的关键信号通路，这些信号通路有助于肿瘤进展和耐药性。它将进一步概述目前处于实体瘤前期和早期临床试验中的 FAKi，以及 FAKi 与化疗相结合的治疗潜力，因为这已成为克服 NSCLC 化疗耐药性的有前途的策略。越来越清楚的是，FAK 不是致癌驱动因素，而是促进肿瘤进展和耐药性。因此，虽然 FAKi 在临床试验中仅表现出有限的结果，但将其他疗法与 FAKi 相结合的治疗方案已显示出克服耐药性的巨大潜力。最后，特别新颖的是 FAK-PROTAC（蛋白水解靶向嵌合体），它独特地靶向胞浆和核 FAK。

NSCLC is the leading cause of cancer-related deaths globally, with a low survival rate primarily due to NSCLC frequently becoming chemoresistant. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in pathways regulating multiple processes in the cell, including survival, migration, and the TME, that contribute to both tumor progression and drug resistance. Recently, FAK inhibitors (FAKi) have shown promising potential for the treatment of NSCLC.This narrative review aims to summarize key signaling pathways involving FAK that contribute to tumor progression and drug resistance. It will further provide an overview of FAKi currently in pre- and early-phase clinical trials for solid tumors, as well as the therapeutic potential of combining FAKi with chemotherapy, as this has emerged as a promising strategy to overcome chemoresistance in NSCLC.It is becoming increasingly clear that FAK is not an oncogenic driver but rather contributes to tumor progression and drug resistance. Hence, while FAKi have only demonstrated modest results in clinical trials when given by themselves, treatment regimens combining other therapies with FAKi have shown promising potential to overcome drug resistance. Lastly, of particular novelty are FAK-PROTACs (proteolysis-targeting chimaeras), which uniquely target both cytosolic and nuclear FAK.