Allosteric therapies for lung cancer

Cancer Metastasis Rev. 2015 Jun;34(2):303-12. doi: 10.1007/s10555-015-9567-z.

Abstract

Allostery is a regulation at a distance by conveying information from one site to another and an intrinsic property of dynamic proteins. Allostery plays an essential role in receptor trafficking, signal transmission, controlled catalysis, gene turn on/off, or cell apoptosis. Allosteric mutations are considered as one of causes responsible for cancer development, leading to "allosteric diseases" by stabilizing an active or inactive conformation or changing the dynamic distribution of preexisting propagation pathways. The present article mainly focuses on the potential of allosteric therapies for lung cancer. Allosteric drugs may have several advantages over traditional drugs. The epidermal growth factor receptor mutations and signaling pathways downstream (such as PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways) were suggested to play a key role in lung cancer and considered as targets of allosteric therapy. Some allosteric inhibitors for lung cancer-specific targets and a series of preclinical trials of allosteric inhibitors for lung cancer have been developed and reported. We expect that allosteric therapies will gain more attentions to develop combinatorial strategies for lung cancer and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation / drug effects*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents