Drug Targets for Skin Cancer

Drug Targets for Skin Cancer

Drug targets for Skin cancer: pharmacology information

Drug targets for Skin cancer: bioreagents

Drug Targets SMO for Skin Cancer with Approved Drugs

Drug targets Cancer drugs Company
SMO vismodegib Roche
SMO sonidegib Novartis

Basal-cell carcinomas (BCCs) are the commonest human cancer. BCC and squamous cell carcinoma are grouped together as non-melanoma skin cancers. Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities. The binding of Sonic hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTCH in basal-cell nevus syndrome. (Xie J, et al. Activating Smoothened mutations in sporadic basal-cell carcinoma[J]. Nature, 1998, 391(6662): 90-92.)

Drug Targets BRAF, MEK for Skin Cancer with Approved Drugs

Drug targets Cancer drugs Company
BRAF Vemurafenib Plexxikon and Genentech
BRAF dabrafenib GlaxoSmithKline
MEK1 MEK2 trametinib
MEK1 MEK2 cobimetinib

Dysregulation of mitogen-activated protein kinase (MAPK) signalling is a hallmark of melanoma and approximately half of all patients with metastatic cutaneous melanoma have a mutation in the BRAF gene. In particular, BRAFV600-mutated melanoma cells are dependent on RAF/MEK/ERK signalling. Based on improved overall survival confirmed in international multicentre randomized phase III trials, two small molecule inhibitors of BRAF, vemurafenib and dabrafenib, and one inhibitor of MEK, trametinib, have been licensed for the treatment of metastatic BRAF mutant melanoma. The combination of dabrafenib plus trametinib is now also being registered for approved use in various countries around the world. (Welsh SJ, et al. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Therapeutic Advances in Medical Oncology. 2015;7(2):122-136.)

Drug Targets PD-1 for Skin Cancer with Approved Drugs

Drug target Cancer drugs Company
PD-1 Pembrolizumab Merck Sharp & Dohme Corp
PD-1 Nivolumab Bristol-Myers Squibb

The PD-1 checkpoints function as a control over immune response hyperactivity. However, these immune checkpoints are also means by which tumors can inhibit T cells and block antitumor immune responses. Interaction between PD-1 and PD-L1 and PD-L2 normally inhibits immune response by reducing T lymphocyte function. Signaling inhibits T cell activation, proliferation, and cytokine production. Many tumors express PD-L1 in order to induce negative regulation of T cells by the PD-1 checkpoint. The anti-PD-1 mAb nivolumab, pembrolizumab has recently been approved by the FDA. These drugs inhibit checkpoint binding of PD-1 and PD-L1 between T cells and the tumor cells, thus inducing immune response. Which may be the new effective treatment for patients with advanced melanoma.

Drug Targets CTLA-4 for Skin Cancer with Approved Drugs

Drug target Cancer drugs Company
CTLA-4 Ipilimumab Bristol-Myers Squibb

CTLA-4, a key negative regulator of T-cell responses, can restrict the antitumor immune response. Ipilimumab (MDX-010) is a fully human, monoclonal antibody that overcomes CTLA-4–mediated T-cell suppression to enhance the immune response against tumors. Preclinical and early clinical studies of patients with advanced melanoma show that ipilimumab promotes antitumor activity as monotherapy and in combination with treatments such as chemotherapy, vaccines, or cytokines. (Weber J. Review: Anti–CTLA-4 antibody ipilimumab: Case studies of clinical response and immune-related adverse events[J]. The oncologist, 2007, 12(7): 864-872.)

Drug targets for Skin cancer: Related Information