The promise of molecular targeted therapies: protein kinase inhibitors in the treatment of cutaneous malignancies.

Overview

A new revolution in cancer therapy has arrived with the development of agents targeting cancer-related protein kinases, critical regulators of malignant behavior. These drugs are selective inhibitors of protein kinases, which mediate most signal transduction pathways in malignant cells and result in increased proliferation, evasion of apoptosis, invasion, and metastasis. Protein kinases are the second largest group of drug targets and they account for 20% to 30% of the drug discovery programs of many biotechnology and pharmaceutical companies. A critical review of the literature is performed, highlighting selective inhibitors of signal transduction molecules involved in nonmelanoma skin cancer, melanoma, dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi's sarcoma, and systemic mastocytosis. Clinical studies were identified by searches of the Proceedings of the American Society of Clinical Oncology Annual Meetings, MedLine, and www.clinicaltrials.gov. Clinical trials of kinase inhibitors in study populations are illustrated, highlighting early results, side effects, and potential improvements in outcomes. Case series and case reports were included for rare diseases. These drugs will have important implications in clinical dermatology, based on their expected frequent use in the treatment of dermatologic malignancies, and their associated cutaneous side effects.