Cyclotherapy: protection of normal cells and unshielding of cancer cells

Cell Cycle. 2002 Nov-Dec;1(6):375-82. doi: 10.4161/cc.1.6.259.

Abstract

Avoidance of apoptosis and mitogen-independent growth are hallmarks of cancer. Mitogen-activated kinases (for example, ErbB1, Raf-1, MEK, PI-3-K, mTOR) can suppress chemotherapy-induced apoptosis in cancer cells. While kinase inhibitors restore susceptibility of cancer cells to apoptosis, they do not necessarily cause growth arrest in cancer cells harboring additional mutations in downstream signaling pathways such as inactivation of Rb and overexpression of c-myc. This article provides a conceptual basis for a novel use of inhibitors of mitogenic kinases. While arresting growth of normal cells, kinase inhibitors may not arrest cancer cells but instead can sensitize them to apoptosis. Following pretreatment with low doses of kinase inhibitors, the chemotherapy that predominantly induces apoptosis in cycling cells (cyclotherapy) will kill cancer cells while sparing normal cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Drug Therapy / methods
  • Drug Therapy / trends
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Genes, cdc / drug effects*
  • Genes, cdc / physiology
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / genetics
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology*
  • Neoplasms / genetics

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors