The Akt signaling pathway: an emerging therapeutic target in malignant melanoma.

Published

Journal Article (Review)

Studies using cultured melanoma cells and patient tumor biopsies have demonstrated deregulated PI3 kinase-Akt3 pathway activity in ~70% of melanomas. Furthermore, targeting Akt3 and downstream PRAS40 has been shown to inhibit melanoma tumor development in mice. Although these preclinical studies and several other reports using small interfering RNAs and pharmacological agents targeting key members of this pathway have been shown to retard melanoma development, analysis of early Phase I and Phase II clinical trials using pharmacological agents to target this pathway demonstrate the need for (1) selection of patients whose tumors have PI3 kinase-Akt pathway deregulation, (2) further optimization of therapeutic agents for increased potency and reduced toxicity, (3) the identification of additional targets in the same pathway or in other signaling cascades that synergistically inhibit the growth and progression of melanoma, and (4) better methods for targeted delivery of pharmaceutical agents inhibiting this pathway. In this review we discuss key potential targets in PI3K-Akt3 signaling, the status of pharmacological agents targeting these proteins, drugs under clinical development, and strategies to improve the efficacy of therapeutic agents targeting this pathway.

Full Text

Duke Authors

Cited Authors

  • Madhunapantula, SV; Mosca, PJ; Robertson, GP

Published Date

  • December 15, 2011

Published In

Volume / Issue

  • 12 / 12

Start / End Page

  • 1032 - 1049

PubMed ID

  • 22157148

Pubmed Central ID

  • 22157148

Electronic International Standard Serial Number (EISSN)

  • 1555-8576

Digital Object Identifier (DOI)

  • 10.4161/cbt.12.12.18442

Language

  • eng

Conference Location

  • United States