Division of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado, USA.
Oncologist. 2011;16(5):566-78. doi: 10.1634/theoncologist.2010-0408. Epub 2011 Apr 26.
Src is believed to play an important role in cancer, and several agents targeting Src are in clinical development.
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 abstracts from major oncology meeting databases in the last 3 years and by comprehensively reviewing ongoing clinical trials on ClinicalTrials.gov.
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.
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.
Src 被认为在癌症中发挥着重要作用，目前已有几种针对 Src 的药物处于临床开发阶段。
我们通过 PubMed 搜索，回顾了 Src 的结构和功能，以及支持其在癌症发展中作用的临床前数据。我们还通过搜索过去 3 年主要肿瘤会议数据库的摘要，并全面审查 ClinicalTrials.gov 上正在进行的临床试验，对 Src 抑制剂进行了广泛的回顾。
在本文中，我们简要回顾了 Src 的结构和功能、涉及导致癌症发生的 Src 的机制，以及 Src 抑制剂和关键的临床前数据，为临床应用提供了依据。然后，我们重点介绍了支持它们在实体瘤恶性肿瘤中应用的临床数据，这是一个比血液学应用更为成熟的新领域。特别强调的是正在研究新的生物标志物的临床试验，以及正在评估生物标志物选择的患者人群中 Src 抑制剂活性的研究。我们还回顾了新的研究性 Src 靶向药物。
Src 抑制剂在未选择的实体瘤患者人群的单药试验中活性有限。正在进行联合研究和基于生物标志物的临床试验。
