The promise of genomics and the development of targeted therapies for cutaneous squamous cell carcinoma

Harwood, C. A., Proby, C. M., Inman, G. J. and Leigh, I. M. (2016) The promise of genomics and the development of targeted therapies for cutaneous squamous cell carcinoma. Acta Dermato Venereologica, 96(1), pp. 3-16. (doi: 10.2340/00015555-2181) (PMID:26084328)

Abstract

Targeted therapies for melanoma and basal cell carcinoma have evolved from deciphering the molecular mechanisms involved in their tumorigenesis. Mutations in BRAF have led to clinical use of BRAF-inhibitors in advanced melanoma, and mutations in Hedgehog signaling to smoothened inhibitors in basal cell carcinoma. The development of tumor resistance to these treatments is leading to many new drug development initiatives and the exploration of multiple signalling pathways. Cutaneous squamous cell carcinoma continues to rise steeply in incidence with very limited therapeutic options for locally advanced or metastatic disease. New genetic technologies find significant levels of mutation in Notch gene family as well as other already recognized gene mutations, such as TP53. The mutational burden in cutaneous squamous cell carcinoma is massive, challenging the identification of driver genes and inhibiting translation from genomics to the clinic. Clinical experience with targeted therapies, such as epidermal growth factor receptor inhibitors, or immune modulatory drugs suggests that these agents may be of benefit to patients, while a more complete understanding of the mechanisms behind squamous cell carcinogenesis awaits further progress.

• Item Type: Articles
• Additional Information: IML, CP and CAH are funded by CRUK programme grant and IML by an ERC advanced investigator award.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Inman, Professor Gareth
• Authors: Harwood, C. A., Proby, C. M., Inman, G. J., and Leigh, I. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Acta Dermato Venereologica
• Publisher: Society for Publication of Acta Dermato-Venereologica
• ISSN: 0001-5555
• ISSN (Online): 1651-2057
• Published Online: 01 January 2016
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Acta Dermato Venereologica 96:3-16
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher