Current Status of Src Inhibitors in Solid Tumor Malignancies

Src is believed to play an important role in cancer, and several agents targeting Src are in clinical development. Design. We reviewed Src structure and function and preclinical data supporting its role in the development of cancer via a PubMed search. We conducted an extensive review of Src inhibitors by searching s from major oncology meeting databases in the last 3 years and by comprehensively reviewing ongoing clinical trials on ClinicalTrials.gov. Results. In this manuscript, we briefly review Src structure and function, mechanisms involving Src that lead to the development of cancer, and Src inhibitors and key preclinical data establishing a rationale for clinical application. We then focus on clinical data supporting their use in solid tumor malignancies, a newer arena than their more well‐established hematologic applications. Particularly highlighted are clinical trials investigating new biomarkers as well as ongoing studies assessing Src inhibitor activity in biomarker‐selected patient populations. We also review newer investigational Src‐targeting agents. Conclusions. Src inhibitors have shown little activity in monotherapy trials in unselected solid tumor patient populations. Combination studies and biomarker‐driven clinical trials are under way. 摘要 概述. Src在癌症中发挥重要作用，几种靶向Src的药物正在临床研究中。 设计. 通过检索PubMed数据库，我们复习了Src的结构和功能以及支持它与癌症发生相关的临床前资料。依据最近3年主要的肿瘤学术会议数据库中的摘要，并全面提取注册于ClinicalTrials.gov的临床试验，我们对Src抑制剂进行了详尽的综述。 结果. 本文简要回顾了Src的结构和功能、致癌的机制和Src抑制剂以及支持其临床应用的关键临床前资料。而后，分析它们在恶性实体瘤中的临床数据，后者较其在血液系统肿瘤中的使用是一个新的领域。我们特别关注那些新的生物标记物驱动的临床试验，以及以生物标记物选择人群进行的评价Src抑制剂活性的临床研究。我们也考察了其他新的正在研究的Src靶向药物。 结论. 在非选择性实体瘤人群中进行的临床试验表明，Src抑制剂的单药治疗活性有限。联合治疗以及生物标志物驱动的临床试验正在进行中。 Src structure and function, mechanisms involving Src that lead to the development of cancer, and key preclinical data establishing a rationale for clinical application are reviewed. Clinical trials investigating new biomarkers as well as ongoing studies assessing Src inhibitor activity in biomarker‐selected patient populations are highlighted.