Targeted Therapy for Cutaneous Oncology: A Review of Novel Treatment Options for Non-Melanoma Skin Cancer: Part I

August 2014 | Volume 13 | Issue 8 | Original Article | 947 | Copyright © 2014

Brooke Walls DO,a Laura Jordan MS4,b Lisa Diaz DO PGY1,b and Richard Miller DO FAOCDc

aLargo Medical Center, Largo, FL
bLake Erie College of Osteopathic Medicine, Bradenton, FL
cBay Dermatology, Palm Harbor, FL

Abstract

The field of cutaneous oncology is exploding with innovative treatment options, specifically in the field of targeted therapy. These advances offer new hope to select patients with high risk skin cancers. Here we provide a two part series reviewing targeted therapy for non-melanoma skin cancer. We begin our discussion with basal cell carcinoma, moving beyond the first-in-class hedgehog inhibitors and highlighting promising clinical trials.

J Drugs Dermatol. 2014;13(8):947-952.

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INTRODUCTION

An evolving theme in the field of cutaneous oncology is the use of personalized or targeted therapy for the treatment of advanced disease. Targeted therapy is the identification of the biomolecular pathways that lead to malignancy and the subsequent targeting and manipulation of these pathways to halt cancer progression. Non-melanoma skin cancers have been at the forefront of this exciting field of cancer genetics and molecular biology. The advent of molecular targeted therapies in oncology offers patients hope and viable alternatives to the traditional chemotherapeutic options that are cytotoxic. Research has elucidated the molecular pathways that cause basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This incredible insight has led to the development of a new armamentarium that can target cancer genomics and halt the progression of disease. Blockade of the hedgehog (Hh) signaling pathway has been a breakthrough in the management of patients with advanced basal cell carcinoma (BCC) as has the use of cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, in advanced squamous cell carcinoma (SCC). Although promising results have been reported, recurrence and evolution of new tumors via circumvention of traditional pathways has occurred. In this review, we discuss the molecular pathways critical to the development of BCC and SCC and the novel pharmacologic agents that have been and are in development to target them. We herein present a two-part review of targeted therapy for non-melanoma skin cancers. Specifically, in part I we will review the use of the hedgehog inhibitors in advanced BCC and continue the theme in part II for epidermal growth factor receptor (EGFR) inhibitors in advanced SCC.

METHODS

We conducted a systematic literature review using the Pubmed data base employing the search terms including: vismodegib,basal cell carcinoma, hedgehog inhibitor, smoothened inhibitor, locally advanced basal cell carcinoma, metastatic basal cell carcinoma, cetuximab, squamous cell carcinoma of the skin, locally advanced squamous cell carcinoma, metastatic squamous cell carcinoma, and epidermal growth factor inhibitors for squamous cell carcinoma of the skin. We then scrutinized citation lists from retrieved articles. We also searched the clinical trials data base at www.clinicaltrials.org using similar search terms. We focused our literature review on clinical trials for advanced skin cancers.

Targeted Therapy for Basal Cell Carcinoma- The Hedgehog Inhibitors

Basal cell carcinoma (BCC) is the most common skin cancer with a lifetime risk of developing BCC in Caucasian populations estimated to be around 25%.1-2 Traditionally, BCC has been considered a carcinoma of the elderly; however, accelerated rates of incidences have been noted, especially in young women aged 20-40 years of age.1 Generally, BCC is considered to be an indolent carcinoma that will continue to grow and cause local tissue destruction. Thus, surgical excision or Mohs micrographic surgery are the standard of care for treatment with high cure rates.3-4 Based on histologic subtype, location, and patient co-factors, other appropriate treatments of localized disease include electrodessication and curettage, cryosurgery, and topical immunotherapy.2-4 Rarely, patients present with locally advanced or metastatic BCCs or, in patients with hereditary basal cell syndromes who accrue hundreds of BCCs over their lifetime, present as treatment dilemmas as standard excision is difficult or unrealistic.5-10 The study of the hereditary basal cell syndromes, especially the basal cell nevus syndrome (BCNS) has contributed greatly to our understanding of the pathogenesis of BCC.11 A molecular understanding of the pathogenesis

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