Characterization of anticancer drug resistance by reverse-phase protein array: new targets and strategies

Ann M. Cathcart, Hannah Smith, Marilyne Labrie, Gordon B. Mills

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Drug resistance is the main barrier to achieving cancer cures with medical therapy. Cancer drug resistance occurs, in part, due to adaptation of the tumor and microenvironment to therapeutic stress at a proteomic level. Reverse-phase protein arrays (RPPA) are well suited to proteomic analysis of drug resistance due to high sample throughput, sensitive detection of phosphoproteins, and validation for a large number of critical cellular pathways. Areas covered: This review summarizes contributions of RPPA to understanding and combating drug resistance. In particular, contributions of RPPA to understanding resistance to PARP inhibitors, BRAF inhibitors, immune checkpoint inhibitors, and breast cancer investigational therapies are discussed. Articles reviewed were identified by MEDLINE, Scopus, and Cochrane search for keywords ‘proteomics,’ ‘reverse-phase protein array,’ ‘drug resistance,’ ‘PARP inhibitor,’ ‘BRAF inhibitor,’ ‘immune checkpoint inhibitor,’ and ‘I-SPY’ spanning October 1, 1960–October 1, 2021. Expert opinion: Precision oncology has thus far failed to convert the armament of targeted therapies into durable responses for most patients, highlighting that genetic sequencing alone is insufficient to guide therapy selection and overcome drug resistance. Combined genomic and proteomic analyses paired with creative drug combinations and dosing strategies hold promise for maturing precision oncology into an era of improved patient outcomes.

Original languageEnglish (US)
Pages (from-to)115-129
Number of pages15
JournalExpert Review of Proteomics
Volume19
Issue number2
DOIs
StatePublished - 2022

Keywords

  • adaptive resistance
  • BRAF inhibitor
  • drug resistance
  • immune checkpoint inhibitor
  • PARP inhibitor
  • precision oncology
  • Proteomics
  • reverse-phase protein array
  • RPPA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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