Review
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Clin Oncol. Mar 10, 2012; 3(3): 32-42
Published online Mar 10, 2012. doi: 10.5306/wjco.v3.i3.32
Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas
Murielle Mimeault, Surinder K Batra
Murielle Mimeault, Surinder K Batra, Department of Biochemistry and Molecular Biology, College of Medicine, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5870, United States
Author contributions: Mimeault M searched and reviewed the literature and wrote the manuscript; Batra SK reviewed the literature and revised the manuscript; both authors read and approved the final version of manuscript.
Supported by The National Institutes of Health National Cancer Institute, Grants EDRN CA111294, and SPORE CA127297
Correspondence to: Murielle Mimeault, PhD, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, United States. mmimeault@unmc.edu
Telephone: +1-402-5595455 Fax: +1-402-5596650
Received: November 6, 2011
Revised: February 12, 2012
Accepted: March 5, 2012
Published online: March 10, 2012
Abstract

Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cell-based therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transformation of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-RafV600E and N-RasQ61R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor (EGFR), stem cell-like factor (SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) and vascular endothelial growth factor (VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition (EMT)-associated molecules, including phosphatidylinositol 3’-kinase (PI3K)/Akt/ molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), macrophage inhibitory cytokine-1 (MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.

Keywords: Cutaneous melanomas; Melanoma stem/progenitor cells; Biomarkers; Screening tests; Diagnosis; Prognosis; Molecular targets; Targeted therapy