Sunitinib and Periodic Hair Depigmentation Due to Temporary c-KIT Inhibition

Chronic lymphocytic leukemia cells receive RAF-dependent survival signals in response to CXCL12 that are sensitive to inhibition by sorafenib

“…Sunitinib is an inhibitor of non-RAF kinases that are also inhibited by sorafenib, 20 including vascular epidermal growth factor receptors, platelet-derived growth factor receptors, Flt3 and c-Kit, but it does not target RAF. 21 As a positive control, the activity of sunitinib in CLL cells was demonstrated by its capacity to block CXCL12-induced activation of cAMP response element-binding in the same experiment (data not shown). Thus, these shared kinase targets are not involved in the activation of MEK after treatment with CXCL12.…”

“…Although originally developed as a RAF inhibitor, sorafenib was subsequently found to inhibit other tyrosine kinases, including vascular epidermal growth factor receptor 2 and 3, platelet derived growth factor receptor-␤, Flt3, and c-Kit. 19 That these kinases do not play a role in the MEK signaling induced by CXCL12 is indicated by the lack of activity on the MEK/ERK pathways of another drug, sunitinib, which inhibits these other kinases, 21 but not RAF. Two other RAF inhibitors also blocked CXCL12-induced activation of MEK/ERK in CLL cells, providing additional support for this model.…”

An indolylquinoline derivative activates DNA damage response and apoptosis in human hepatocellular carcinoma cells

“…Another approved drug sunitinib for treatment is a multi-targeted receptor tyrosine kinase inhibitor. The drug blocks the tyrosine kinase activities of KIT, PDGFR, VEGFR2 and other tyrosine kinases during tumor development (11). Most traditional chemotherapy exhibited low response rate in curing HCC (12).…”

Cutaneous Adverse Effects Associated With the Tyrosine-Kinase Inhibitor Cabozantinib

“…Patients receiving long-term cabozantinib therapy, therefore, may develop increased photosensitivity and should be advised of this risk and appropriate UV-protective measures. Hair and skin depigmentation is also observed in association with sunitinib and imatinib, 34–38 particularly in heavily pigmented skin, and is reversible within a few weeks of discontinuing therapy. Patients who receive sunitinib in a cyclic manner develop alternating horizontal bands of depig-mented and normal hair resulting in a characteristic striped appearance.…”