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Activation of the PI3K/Akt pathway and chemotherapeutic resistance.

Publication ,  Journal Article
West, KA; Castillo, SS; Dennis, PA
Published in: Drug Resist Updat
December 2002

The resistance of many types of cancer to conventional chemotherapies is a major factor undermining successful cancer treatment. In this review, the role of a signal transduction pathway comprised of the lipid kinase, phosphatidylinositol 3-kinase (PI3K), and the serine/threonine kinase, Akt (or PKB), in chemotherapeutic resistance will be explored. Activation of this pathway plays a pivotal role in essential cellular functions such as survival, proliferation, migration and differentiation that underlie the biology of human cancer. Akt activation also contributes to tumorigenesis and tumor metastasis, and as shown most recently, resistance to chemotherapy. Modulating Akt activity is now a commonly observed endpoint of chemotherapy administration or administration of chemopreventive agents. Studies performed in vitro and in vivo combining small molecule inhibitors of the PI3K/Akt pathway with standard chemotherapy have been successful in attenuating chemotherapeutic resistance. As a result, small molecules designed to specifically target Akt and other components of the pathway are now being developed for clinical use as single agents and in combination with chemotherapy to overcome therapeutic resistance. Specifically inhibiting Akt activity may be a valid approach to treat cancer and increase the efficacy of chemotherapy.

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Published In

Drug Resist Updat

DOI

ISSN

1368-7646

Publication Date

December 2002

Volume

5

Issue

6

Start / End Page

234 / 248

Location

Scotland

Related Subject Headings

  • Retroviridae Proteins, Oncogenic
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Oncology & Carcinogenesis
  • Oncogene Protein v-akt
  • Neoplasms
  • Humans
  • Enzyme Inhibitors
  • Enzyme Activation
  • Drug Resistance, Neoplasm
 

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West, K. A., Castillo, S. S., & Dennis, P. A. (2002). Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updat, 5(6), 234–248. https://doi.org/10.1016/s1368-7646(02)00120-6
West, Kip A., S Sianna Castillo, and Phillip A. Dennis. “Activation of the PI3K/Akt pathway and chemotherapeutic resistance.Drug Resist Updat 5, no. 6 (December 2002): 234–48. https://doi.org/10.1016/s1368-7646(02)00120-6.
West KA, Castillo SS, Dennis PA. Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updat. 2002 Dec;5(6):234–48.
West, Kip A., et al. “Activation of the PI3K/Akt pathway and chemotherapeutic resistance.Drug Resist Updat, vol. 5, no. 6, Dec. 2002, pp. 234–48. Pubmed, doi:10.1016/s1368-7646(02)00120-6.
West KA, Castillo SS, Dennis PA. Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updat. 2002 Dec;5(6):234–248.
Journal cover image

Published In

Drug Resist Updat

DOI

ISSN

1368-7646

Publication Date

December 2002

Volume

5

Issue

6

Start / End Page

234 / 248

Location

Scotland

Related Subject Headings

  • Retroviridae Proteins, Oncogenic
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Oncology & Carcinogenesis
  • Oncogene Protein v-akt
  • Neoplasms
  • Humans
  • Enzyme Inhibitors
  • Enzyme Activation
  • Drug Resistance, Neoplasm