Sphingolipid/Ceramide Pathways and Autophagy in the Onset and Progression of Melanoma: Novel Therapeutic Targets and Opportunities

Int J Mol Sci. 2019 Jul 12;20(14):3436. doi: 10.3390/ijms20143436.

Abstract

Melanoma is a malignant tumor deriving from neoplastic transformation of melanocytes. The incidence of melanoma has increased dramatically over the last 50 years. It accounts for most cases of skin cancer deaths. Early diagnosis leads to remission in 90% of cases of melanoma; conversely, for melanoma at more advanced stages, prognosis becomes more unfavorable also because dvanced melanoma is often resistant to pharmacological and radiological therapies due to genetic plasticity, presence of cancer stem cells that regenerate the tumor, and efficient elimination of drugs. This review illustrates the role of autophagy in tumor progression and resistance to therapy, focusing on molecular targets for future drugs.

Keywords: acid ceramidase; autophagy; ceramides; melanoma; multidrug resistance; sphingolipids.

Publication types

  • Review

MeSH terms

  • Acid Ceramidase / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Autophagy* / drug effects
  • Biomarkers, Tumor
  • Cell Transformation, Neoplastic / metabolism*
  • Ceramides / metabolism*
  • Disease Progression
  • Disease Susceptibility*
  • Drug Resistance, Neoplasm
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lipid Metabolism
  • Melanoma / etiology
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Melanoma / therapy
  • Signal Transduction* / drug effects
  • Sphingolipids / metabolism*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Ceramides
  • Sphingolipids
  • ASAH1 protein, human
  • Acid Ceramidase