Kopetz Scott, Shah Ami N, Gallick Gary E
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
Clin Cancer Res. 2007 Dec 15;13(24):7232-6. doi: 10.1158/1078-0432.CCR-07-1902.
Aberrant activation of members of the Src family of nonreceptor protein tyrosine kinases is common in solid tumor malignancies and may contribute to the development and/or progression of these tumors. As a result, four Src inhibitors are now in more than 50 clinical trials for at least 14 different types of solid tumors. In this review, we briefly discuss the preclinical rationale for Src inhibitors, the development strategies most likely to be successful in the clinic, and the rationale for Src inhibitors in combination with other agents as part of a more comprehensive therapeutic strategy. As the use of Src family inhibitors in clinical trials on solid tumors is in its infancy, further studies on the roles of Src family kinases in tumor progression, chemoresistance, epidermal-to-mesenchymal transition, and other properties of tumor progression will be important in designing the most effective clinical trials using these inhibitors.
非受体蛋白酪氨酸激酶Src家族成员的异常激活在实体瘤恶性肿瘤中很常见，可能有助于这些肿瘤的发生和/或进展。因此，四种Src抑制剂目前正在针对至少14种不同类型的实体瘤进行50多项临床试验。在本综述中，我们简要讨论Src抑制剂的临床前理论依据、在临床上最有可能成功的开发策略，以及Src抑制剂与其他药物联合使用作为更全面治疗策略一部分的理论依据。由于Src家族抑制剂在实体瘤临床试验中的应用尚处于起步阶段，进一步研究Src家族激酶在肿瘤进展、化疗耐药性、上皮-间质转化及肿瘤进展的其他特性中的作用，对于设计使用这些抑制剂的最有效临床试验至关重要。
