Rationale-based therapeutic combinations with PI3K inhibitors in cancer treatment

Pau Castel, Eneda Toska, Zachary S. Zumsteg, F. Javier Carmona, Moshe Elkabets, Ana Bosch, Maurizio Scaltriti

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The PI3K/AKT/mTOR signaling is important for cell proliferation, survival, and metabolism. Hyperactivation of this pathway is one of the most common signaling abnormalities observed in cancer and a substantial effort has recently been made to develop molecules targeting this signaling cascade. However, it is becoming evident that PI3K inhibitors used as single agents do not elicit dramatic or durable responses. Given the numerous mechanisms mediating intrinsic and acquired resistance to these agents, hypothesis-based combinatorial strategies are probably needed to fully exploit their antitumor activity. In the first part of this review, we briefly dissect the PI3K/AKT/mTOR axis and list the most advanced compounds targeting different nodes of this cascade. The second part focuses on what we believe to be the most promising rationale-based therapeutic combinations with PI3K/AKT/mTOR inhibitors in solid tumors, with special emphasis on breast cancer.

Original languageEnglish
Article numbere963447
JournalMolecular and Cellular Oncology
Volume1
Issue number3
DOIs
StatePublished - 15 Sep 2014
Externally publishedYes

Keywords

  • AKT
  • PIK3CA
  • PTEN
  • resistance
  • targeted therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Cancer Research

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