Activation of the PI3K/Akt pathway and chemotherapeutic resistance

Kip A. West, S. Sianna Castillo, Phillip A. Dennis

Research output: Contribution to journalArticle

Abstract

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. Published by Elsevier Science Ltd..

Original languageEnglish (US)
Pages (from-to)234-248
Number of pages15
JournalDrug Resistance Updates
Volume5
Issue number6
DOIs
StatePublished - Dec 2002
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinase
Drug Therapy
Neoplasms
Protein-Serine-Threonine Kinases
Combination Drug Therapy
Signal Transduction
Carcinogenesis
Phosphotransferases
Neoplasm Metastasis
Lipids
Survival
Therapeutics

Keywords

  • Akt
  • Apoptosis
  • Cancer
  • Chemotherapy
  • Kinase

ASJC Scopus subject areas

  • Cancer Research
  • Infectious Diseases
  • Oncology
  • Pharmaceutical Science

Cite this

Activation of the PI3K/Akt pathway and chemotherapeutic resistance. / West, Kip A.; Castillo, S. Sianna; Dennis, Phillip A.

In: Drug Resistance Updates, Vol. 5, No. 6, 12.2002, p. 234-248.

Research output: Contribution to journalArticle

West, Kip A. ; Castillo, S. Sianna ; Dennis, Phillip A. / Activation of the PI3K/Akt pathway and chemotherapeutic resistance. In: Drug Resistance Updates. 2002 ; Vol. 5, No. 6. pp. 234-248.
@article{d2ec8f25c20846dd9356dabac606b3be,
title = "Activation of the PI3K/Akt pathway and chemotherapeutic resistance",
abstract = "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. Published by Elsevier Science Ltd..",
keywords = "Akt, Apoptosis, Cancer, Chemotherapy, Kinase",
author = "West, {Kip A.} and Castillo, {S. Sianna} and Dennis, {Phillip A.}",
year = "2002",
month = "12",
doi = "10.1016/S1368-7646(02)00120-6",
language = "English (US)",
volume = "5",
pages = "234--248",
journal = "Drug Resistance Updates",
issn = "1368-7646",
publisher = "Churchill Livingstone",
number = "6",

}

TY - JOUR

T1 - Activation of the PI3K/Akt pathway and chemotherapeutic resistance

AU - West, Kip A.

AU - Castillo, S. Sianna

AU - Dennis, Phillip A.

PY - 2002/12

Y1 - 2002/12

N2 - 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. Published by Elsevier Science Ltd..

AB - 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. Published by Elsevier Science Ltd..

KW - Akt

KW - Apoptosis

KW - Cancer

KW - Chemotherapy

KW - Kinase

UR - http://www.scopus.com/inward/record.url?scp=0036968347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036968347&partnerID=8YFLogxK

U2 - 10.1016/S1368-7646(02)00120-6

DO - 10.1016/S1368-7646(02)00120-6

M3 - Article

VL - 5

SP - 234

EP - 248

JO - Drug Resistance Updates

JF - Drug Resistance Updates

SN - 1368-7646

IS - 6

ER -