Muscarinic receptor agonists and antagonists: Effects on cancer

Research output: Chapter in Book/Report/Conference proceedingChapter

75 Scopus citations

Abstract

Many epithelial and endothelial cells express a cholinergic autocrine loop in which acetylcholine acts as a growth factor to stimulate cell growth. Cancers derived from these tissues similarly express a cholinergic autocrine loop and ACh secreted by the cancer or neighboring cells interacts with M3 muscarinic receptors expressed on the cancer cells to stimulate tumor growth. Primary proliferative pathways involve MAPK and Akt activation. The ability of muscarinic agonists to stimulate, and M3 antagonists to inhibit tumor growth has clearly been demonstrated for lung and colon cancer. The ability of muscarinic agonists to stimulate growth has been shown for melanoma, pancreatic, breast, ovarian, prostate and brain cancers, suggesting that M3 antagonists will also inhibit growth of these tumors as well. As yet no clinical trials have proven the efficacy of M3 antagonists as cancer therapeutics, though the widespread clinical use and low toxicity of M3 antagonists support the potential role of these drugs as adjuvants to current cancer therapies.

Original languageEnglish (US)
Title of host publicationMuscarinic Receptors
EditorsAllison D. Fryer, Neil M. Nathanson, Arthur Christopoulos
Pages451-468
Number of pages18
DOIs
StatePublished - 2012

Publication series

NameHandbook of Experimental Pharmacology
Volume208
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Keywords

  • Acetylcholine
  • Colon cancer
  • Lung cancer
  • M3 muscarinic receptor
  • Muscarinic receptors
  • Therapy

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

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