Genitourinary Center, M.D. Anderson Cancer Centre, Houston, TX 77030, USA.
Cancer Treat Rev. 2010 Oct;36(6):492-500. doi: 10.1016/j.ctrv.2010.02.015. Epub 2010 Mar 11.
SRC is a tyrosine kinase that plays a role in oncogenic, invasive and bone-metastatic processes. It has therefore been prioritized as a candidate therapeutic target in patients with solid tumors. Several SRC inhibitors are now in development, of which dasatinib has been most explored. Preclinical studies in a wide variety of solid tumor cell lines, including prostate, breast and glioma, have shown that that dasatinib acts as a cytostatic agent, inhibiting the processes of cell proliferation, invasion and metastasis. Dasatinib also inhibits the activity of osteoclasts, which have a major role in the development of metastatic bone lesions. Dasatinib has additive or synergistic activity in combination with a number of other agents, including cytotoxic agents and targeted therapies, providing a rationale for combination treatment in a clinical setting. Emerging clinical data with dasatinib support experimental observations, with preliminary phase 1 and 2 data demonstrating activity, both as a single agent and as combination therapy, in a range of solid tumors. Future clinical trials will further assess the clinical value of SRC inhibition with dasatinib.
SRC 是一种酪氨酸激酶，在致癌、侵袭和骨转移过程中发挥作用。因此，它已被优先作为实体瘤患者的候选治疗靶点。目前有几种 SRC 抑制剂正在开发中，其中达沙替尼的研究最为深入。广泛的实体瘤细胞系（包括前列腺癌、乳腺癌和神经胶质瘤）的临床前研究表明，达沙替尼作为一种细胞生长抑制剂，可抑制细胞增殖、侵袭和转移过程。达沙替尼还抑制破骨细胞的活性，破骨细胞在转移性骨病变的发展中起主要作用。达沙替尼与许多其他药物联合使用具有相加或协同作用，包括细胞毒性药物和靶向治疗药物，为临床联合治疗提供了依据。达沙替尼的临床数据支持实验观察结果，初步的 1 期和 2 期数据表明，达沙替尼在多种实体瘤中具有作为单一药物和联合治疗的活性。未来的临床试验将进一步评估达沙替尼抑制 SRC 的临床价值。
