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

August 2014 | Volume 13 | Issue 8 | Original Article | 955 | 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. In part two of our series on targeted therapy for skin cancer, we focus our attention on squamous cell carcinoma. We begin with the epidermal growth factor receptor inhibitors and branch out into newer areas of active research.

J Drugs Dermatol. 2014;13(8):955-958.

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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 Advanced Squamous Cell Carcinoma of the Skin; the Epidermal Growth Factor Receptors and Beyond Introduction

Squamous Cell Carcinoma of the skin (SCCS) is the second most common type of skin cancer, and similar to other non-melanoma and melanoma skin cancers, the incidence continues to rise. SCCS is typically found in elderly individuals in ultravioletexposed regions of the body. It tends to be more common in individuals with fair complexions and those with a compromised immune system, especially solid organ transplant recipients.1-5 While both BCC and SCCS commonly occur from chronic UV radiation, the genomics of cancer development differ. SCCS follows a methodical process from precancerous actinic keratosis (AK) to pre-invasive carcinoma in situ to invasive SCCS.6 In addition, SCCS tends to behave more aggressively, with higher rates of recurrence, metastasis, and mortality compared to BCC.7 Advanced SCCS is rare and can be defined as: 1) locally unresectable, deeply invasive (involving muscle, nerve, or bone), 2) unresectable regional nodal disease, and/or 3) occurrence of multiple distant metastases. Advanced SCCS have a rate of recurrence or metastasis of 20-25% during the first 2 years of diagnosis.3,8 When localized to the skin, topical treatment with

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