Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors

Abstract

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.

Figure 1

During bone metastasis, systemic factors within the bone environment and bone-derived growth factors activate the release of factors from metastatic tumor cells that stimulate osteoclast activity. Because SRC signaling has a central role in tumor cell and osteoclast function, the ability of dasatinib to inhibit SRC activity has a potential role in the prevention of osteolytic metastases [adapted from ].