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Peptide receptors as cancer drug targets

Terry W Moody1

  • 1Department of Health and Human Services, Center for Cancer Training, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Annals of the New York Academy of Sciences
|May 11, 2019
PubMed

Insights

Neuropeptides like bombesin and VIP, acting through G protein-coupled receptors (GPCRs), stimulate small cell lung cancer (SCLC) growth. Targeting these GPCRs offers a promising strategy for SCLC early detection and treatment.

Area of Science:

  • Oncology
  • Neuroendocrinology
  • Molecular Biology

Background:

  • Neuropeptides act as neuromodulators by binding to G protein-coupled receptors (GPCRs).
  • In cancer cells, neuropeptides can function in an autocrine manner, stimulating tumor growth.
  • Small cell lung cancer (SCLC) cells synthesize and secrete bombesin (BB)-like peptides and vasoactive intestinal peptide (VIP).

Purpose of the Study:

  • To review the role of GPCRs for VIP and BB in SCLC.
  • To explore the potential of these GPCRs as molecular targets for cancer detection and treatment.

Main Methods:

  • The review synthesizes existing research on neuropeptide signaling in SCLC.
  • Focuses on the mechanisms of BB-like peptides and VIP binding to their respective receptors (BBRs and VIPRs).
  • Examines downstream signaling pathways including ERK, cAMP, and CREB.

Main Results:

  • BB-like peptides bind to BBRs, activating signaling pathways that promote SCLC cell growth.
  • VIP binding to VIPRs increases BB-like peptide release, further stimulating SCLC proliferation.
  • Antagonists for BBR and VIPR have demonstrated inhibition of SCLC growth.

Conclusions:

  • GPCRs for VIP and BB are crucial in regulating SCLC proliferation.
  • Targeting these GPCRs represents a viable strategy for the early detection and therapeutic intervention of SCLC.
Keywords:
CREBbombesincancerpeptide receptorsvasoactive intestinal peptide

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