Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors.
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.
Genitourinary Center, M.D. Anderson Cancer Centre, Houston, TX 77030, USA. johna@mdanderson.org
John
J
Araujo
Christopher
C
Logothetis
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D000069439:Dasatinib; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000187:drug effects
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D019061:src-Family Kinases; D000069439:Dasatinib