Princess Margaret Hospital/Ontario Cancer Institute (PMH/OCI), Toronto M5G 2M9, Ontario, Canada.
Expert Opin Ther Targets. 2010 Jan;14(1):77-94. doi: 10.1517/14728220903460340.
Focal adhesion kinase (FAK), a crucial mediator of integrin and growth factor signaling, is a novel and promising target in cancer therapy. FAK resides within focal adhesions which are contact points between extracellular matrix (ECM) and cytoskeleton, and increased expression of the kinase has been linked with cancer cell migration, proliferation and survival. The aim of this review is to summarize the current research in the area and to assess the potential of different FAK-targeting strategies for cancer therapy.
We briefly examine the evidence pointing towards FAK as potential anti-cancer target since its discovery in 1992. Then, we summarize different approaches developed to interfere with FAK signaling and important results reported from these experiments. Finally, we discuss the potential of these strategies to accomplish inhibition of tumor growth and distant spread as well as potentially meaningful combinations with other therapeutic modalities in the context of the currently available evidence.
The review emphasizes the link between FAK biology and the consequences of interference with FAK signaling. Based on this foundation an opinion is formed with regard to the future of FAK as therapeutic target.
Inhibition of FAK harbours the potential to restrain malignant growth and progression with minimal side effects in normal tissues. Small molecule inhibitors of the kinase should be examined in further clinical studies and combinations with existing therapies need to be explored. More efforts are required to identify markers which predict response towards FAK inhibition.
粘着斑激酶（FAK）是整合素和生长因子信号的关键介质，是癌症治疗中的一个新的有前途的靶点。FAK 位于粘着斑内，是细胞外基质（ECM）和细胞骨架之间的接触点，激酶的表达增加与癌细胞的迁移、增殖和存活有关。本综述的目的是总结这一领域的现有研究，并评估不同 FAK 靶向策略在癌症治疗中的潜力。
自 1992 年发现 FAK 以来，我们简要地研究了指向 FAK 作为潜在抗癌靶点的证据。然后，我们总结了为干扰 FAK 信号而开发的不同方法，并总结了这些实验报告的重要结果。最后，我们讨论了这些策略在目前可用证据的背景下抑制肿瘤生长和远处扩散以及与其他治疗方式的潜在有意义的组合的潜力。
该综述强调了 FAK 生物学与干扰 FAK 信号的后果之间的联系。在此基础上，对 FAK 作为治疗靶点的未来形成了意见。
抑制 FAK 有可能在正常组织中产生最小的副作用，从而抑制恶性生长和进展。应在进一步的临床研究中检查激酶的小分子抑制剂，并探索与现有疗法的联合应用。需要更多的努力来识别预测 FAK 抑制反应的标志物。
