PI3 kinase activation and response to Trastuzumab Therapy: what's neu with herceptin resistance?

Cancer Cell. 2007 Oct;12(4):297-9. doi: 10.1016/j.ccr.2007.10.004.

Abstract

Trastuzumab is an established therapy for women with breast cancers that overexpress HER2. Despite its proven benefit in treating breast cancer, not all women derive benefit from this monoclonal antibody, and resistant disease can develop. In this issue of Cancer Cell, Berns et al. present evidence that activation of the PI3 kinase pathway, either via loss of the tumor suppressor PTEN or through oncogenic stimulation of PIK3CA, can mediate trastuzumab resistance. This study extends important work of others and forms the rationale for future investigations combining inhibitors of the PI3 kinase pathway in conjunction with trastuzumab therapy.

Publication types

  • Comment

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Class I Phosphatidylinositol 3-Kinases
  • Disease Progression
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Patient Selection
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Trastuzumab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • RNA, Small Interfering
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Trastuzumab