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Proteomics approaches to understanding mitogen-activated protein kinase inhibitor resistance in melanoma

Verena Paulitschke1, Ossia Eichhoff, Phil F Cheng

  • 1aDepartment of Dermatology, Medical University of Vienna, Vienna, Austria bInstitute of Molecular Systems Biology, ETH Zurich, Switzerland cDepartment of Dermatology, University of Zurich Hospital, University of Zurich, Zurich, Switzerland.

Current Opinion in Oncology
|January 8, 2016
PubMed
Abstract

Insights

Proteomics reveals mechanisms of BRAF inhibitor resistance in melanoma. Melanoma cells adapt to targeted therapy by becoming invasive, highlighting the need for new treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • BRAF inhibitors (BRAFi) are effective against BRAF-mutated melanoma but resistance is a significant clinical challenge.
  • Melanoma's plasticity and heterogeneity contribute to therapeutic resistance, necessitating advanced analytical approaches.
  • Proteomics offers complementary insights beyond genomics to understand melanoma progression during treatment.

Purpose of the Study:

  • To explore the role of proteomics in understanding mitogen-activated protein kinase inhibitor (MAPKi) resistance in melanoma.
  • To identify pathophysiological mechanisms driving melanoma progression under targeted therapy using proteomic approaches.

Main Methods:

  • Review of proteomics studies investigating MAPKi resistance.
  • Description of technologies including shotgun analysis, pressure cycling technology-sequential window acquisition of all theoretical masses, and selected reaction monitoring.
  • Analysis of preliminary data linking protein expression changes to drug resistance.

Main Results:

  • Melanoma cells undergoing MAPKi treatment exhibit phenotypic changes from proliferative to invasive states.
  • Acquisition of epithelial-mesenchymal transformation features is associated with acquired drug resistance.
  • Preliminary findings suggest BRAFi resistance correlates with increased expression in the lysosomal compartment and cell adhesion pathways.

Conclusions:

  • Proteomics can enhance the understanding of MAPKi resistance mechanisms in melanoma.
  • Proteomic insights may guide the development of novel therapeutic strategies.
  • Selected reaction monitoring holds potential for evaluating predictive biomarkers and early detection of resistance.

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