University of South Florida College of Medicine, 12902 Magnolia Drive, MCC-GME, Tampa, Florida 33612, USA.
Expert Opin Investig Drugs. 2010 Mar;19(3):415-25. doi: 10.1517/13543781003592097.
Dasatinib is an oral, potent adenosine triphosphate-competitive inhibitor of multiple tyrosine kinases including BCR-ABL, c-KIT, platelet-derived growth factor receptor, and Src family kinases (SFKs). It has gained much attention for its use in chronic myeloid leukemia and for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. However, dasatinib is also being explored in solid tumors in ongoing Phase I and II clinical trials.
The clinical efficacy of dasatinib in a wide variety of solid tumors and important Phase I/II studies utilizing dasatinib and the optimal dosage used in solid tumors. A literature search was conducted using PubMed/MEDLINE, www.clinicaltrials.gov , and the American Society of Clinical Oncology websites to find relevant Phase I/II clinical trials during 1987-2009.
The understanding that the biology and mechanism of Src activation in tumors are not well understood and finding the optimal use of SFK inhibitors in the clinical setting requires further investigation.
In reviewing the clinical safety data of dasatinib in its current use as a Src inhibitor in a wide variety of solid malignancies, dasatinib appears to be safe and is a promising agent for the treatment of metastatic solid tumors refractory to standard therapies.
达沙替尼是一种口服、强效三磷酸腺苷竞争性抑制剂，可抑制多种酪氨酸激酶，包括 BCR-ABL、c-KIT、血小板衍生生长因子受体和Src 家族激酶（SFKs）。它在慢性髓性白血病的治疗中得到了广泛关注，并用于治疗费城染色体阳性的成人急性淋巴细胞白血病。然而，达沙替尼也正在进行中的 I 期和 II 期临床试验中探索用于实体瘤。
达沙替尼在广泛的实体瘤中的临床疗效，以及利用达沙替尼进行的重要 I/II 期研究，和在实体瘤中使用的最佳剂量。通过使用 PubMed/MEDLINE、www.clinicaltrials.gov 和美国临床肿瘤学会网站进行文献检索，以查找 1987 年至 2009 年期间相关的 I/II 期临床试验。
了解肿瘤中Src 激活的生物学和机制尚不清楚，并且需要进一步研究在临床环境中使用 SFK 抑制剂的最佳方法。
在审查达沙替尼目前作为一种 Src 抑制剂在广泛的各种实体恶性肿瘤中的临床安全性数据时，达沙替尼似乎是安全的，并且是治疗对标准疗法耐药的转移性实体瘤的有前途的药物。
