Overview of the relevance of PI3K pathway in HR-positive breast cancer

Ann Oncol. 2019 Dec 1;30(Suppl_10):x3-x11. doi: 10.1093/annonc/mdz281.

Abstract

One of the hallmarks of hormone receptor (HR)-positive breast cancer is its dependence on the phosphatidylinositol-3-kinase (PI3K) pathway. Here, we review the epidemiologic, functional, and pharmacologic interactions between oncogenic PI3K and the estrogen receptor (ER). We discuss the epidemiology of PI3K pathway alterations, mechanisms of resistance to PI3K inhibitors, and the current mechanistic landscape of crosstalk between PI3K and ER, which provide the rationale for dual ER and PI3K inhibition and is now a standard of care in the treatment of ER+ PIK3CA-mutant metastatic breast cancer. We outline newer studies in this field that delineate the clinically relevant overlaps between PI3K and parallel signaling pathways, insulin signaling, and ER epigenetic modifiers. We also identify several caveats with the current data and propose new strategies to overcome these bottlenecks.

Keywords: PIK3CA; AKT; PI3K inhibitors; PI3K pathway; breast cancer; estrogen receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Drug Resistance, Neoplasm
  • Estrogen Receptor Modulators / administration & dosage
  • Estrogen Receptor Modulators / pharmacology
  • Female
  • Humans
  • Molecular Epidemiology
  • Molecular Targeted Therapy
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors / administration & dosage
  • Phosphoinositide-3 Kinase Inhibitors / pharmacology
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / metabolism*
  • Signal Transduction / drug effects

Substances

  • Estrogen Receptor Modulators
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Estrogen