DDR1 and DDR2: a review on signaling pathway and small molecule inhibitors as an anticancer agent

Abstract

Cancer is the 2nd most fatal disease around the globe. Various receptors have been showed to be overexpressed and/or mutated in numerous cancers. Discoidin domain receptors 1 (DDR1) and 2 (DDR2) are one of the novel receptor tyrosine kinases (RTKs), which have been proved to regulate various cellular signaling pathways, cell proliferation, adhesion, migration, matrix remodeling, and dysregulation of these receptors may lead to metastatic cancer progressions. These receptors belong to unique category of RTKs, which require collagen binding for its activation. Yet the mechanism of this extracellular collagen binding and activation of cytosolic kinase domain of the receptors is not clear. Like other RTKs, these receptors also showed its extensive implications in numerous cancers like lung, breast, ovarian, pancreatic cancer and many others. Therefore DDR1 and DDR2 emerge as potential therapeutic targets in preventing cancer. Various small molecule tyrosine kinase inhibitors have been developed against these two receptors and proved to be highly efficacious in reducing tumor progressions. This review would highlight the detailed structure, functions, mechanism of action, signaling pathways of DDR1 and DDR2, their roles in cancer developments and the inhibition of these receptors with numerous inhibitors can be a promising strategy to combat this hefty menace.