Using Reverse Phase Protein Array (RPPA) to Identify and Target Adaptive Resistance

Marilyne Labrie, Yong Fang, Nicholas D. Kendsersky, Jun Li, Han Liang, Shannon N. Westin, Zahi Mitri, Gordon B. Mills

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Tumor cells and the tumor ecosystem rapidly evolve in response to therapy. This tumor evolution results in the rapid emergence of drug resistance that limits the magnitude and duration of response to therapy including chemotherapy, targeted therapy, and immunotherapy. Thus, there is an urgent need to understand and interdict tumor evolution to improve patient benefit to therapy. Reverse phase protein array (RPPA) provides a powerful tool to evaluate and develop approaches to target the processes underlying one form of tumor evolution: adaptive evolution. Tumor cells and the tumor microenvironment rapidly evolve through rewiring of protein networks to bypass the effects of therapy. In this review, we present the concepts underlying adaptive resistance and use of RPPA in understanding resistance mechanisms and identification of effective drug combinations. We further demonstrate that this novel information is resulting in biomarker-driven trials aimed at targeting adaptive resistance and improving patient outcomes.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages251-266
Number of pages16
DOIs
StatePublished - 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1188
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Adaptive resistance
  • Combination therapy
  • Reverse phase protein array
  • Targeted therapy
  • Tumor evolution

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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