Cargando…

Therapeutic Implications of Targeting AKT Signaling in Melanoma

Identification of key enzymes regulating melanoma progression and drug resistance has the potential to lead to the development of novel, more effective targeted agents for inhibiting this deadly form of skin cancer. The Akt3, also known as protein kinase B gamma, pathway enzymes regulate diverse cel...

Descripción completa

Detalles Bibliográficos
Autores principales: Madhunapantula, SubbaRao V., Robertson, Gavin P.
Formato: Texto
Lenguaje:English
Publicado: SAGE-Hindawi Access to Research 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065045/
https://www.ncbi.nlm.nih.gov/pubmed/21461351
http://dx.doi.org/10.4061/2011/327923
_version_ 1782200944450076672
author Madhunapantula, SubbaRao V.
Robertson, Gavin P.
author_facet Madhunapantula, SubbaRao V.
Robertson, Gavin P.
author_sort Madhunapantula, SubbaRao V.
collection PubMed
description Identification of key enzymes regulating melanoma progression and drug resistance has the potential to lead to the development of novel, more effective targeted agents for inhibiting this deadly form of skin cancer. The Akt3, also known as protein kinase B gamma, pathway enzymes regulate diverse cellular processes including proliferation, survival, and invasion thereby promoting the development of melanoma. Accumulating preclinical evidence demonstrates that therapeutic agents targeting these kinases alone or in combination with other pathway members could be effective for the long-term treatment of advanced-stage disease. However, currently, no selective and effective therapeutic agent targeting these kinases has been identified for clinical use. This paper provides an overview of the key enzymes of the PI3K pathway with emphasis placed on Akt3 and the negative regulator of this kinase called PTEN (phosphatase and tensin homolog deleted on chromosome 10). Mechanisms regulating these enzymes, their substrates and therapeutic implications of targeting these proteins to treat melanoma are also discussed. Finally, key issues that remain to be answered and future directions for interested researchers pertaining to this signaling cascade are highlighted.
format Text
id pubmed-3065045
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher SAGE-Hindawi Access to Research
record_format MEDLINE/PubMed
spelling pubmed-30650452011-03-31 Therapeutic Implications of Targeting AKT Signaling in Melanoma Madhunapantula, SubbaRao V. Robertson, Gavin P. Enzyme Res Review Article Identification of key enzymes regulating melanoma progression and drug resistance has the potential to lead to the development of novel, more effective targeted agents for inhibiting this deadly form of skin cancer. The Akt3, also known as protein kinase B gamma, pathway enzymes regulate diverse cellular processes including proliferation, survival, and invasion thereby promoting the development of melanoma. Accumulating preclinical evidence demonstrates that therapeutic agents targeting these kinases alone or in combination with other pathway members could be effective for the long-term treatment of advanced-stage disease. However, currently, no selective and effective therapeutic agent targeting these kinases has been identified for clinical use. This paper provides an overview of the key enzymes of the PI3K pathway with emphasis placed on Akt3 and the negative regulator of this kinase called PTEN (phosphatase and tensin homolog deleted on chromosome 10). Mechanisms regulating these enzymes, their substrates and therapeutic implications of targeting these proteins to treat melanoma are also discussed. Finally, key issues that remain to be answered and future directions for interested researchers pertaining to this signaling cascade are highlighted. SAGE-Hindawi Access to Research 2011-03-23 /pmc/articles/PMC3065045/ /pubmed/21461351 http://dx.doi.org/10.4061/2011/327923 Text en Copyright © 2011 S. V. Madhunapantula and G. P. Robertson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Madhunapantula, SubbaRao V.
Robertson, Gavin P.
Therapeutic Implications of Targeting AKT Signaling in Melanoma
title Therapeutic Implications of Targeting AKT Signaling in Melanoma
title_full Therapeutic Implications of Targeting AKT Signaling in Melanoma
title_fullStr Therapeutic Implications of Targeting AKT Signaling in Melanoma
title_full_unstemmed Therapeutic Implications of Targeting AKT Signaling in Melanoma
title_short Therapeutic Implications of Targeting AKT Signaling in Melanoma
title_sort therapeutic implications of targeting akt signaling in melanoma
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065045/
https://www.ncbi.nlm.nih.gov/pubmed/21461351
http://dx.doi.org/10.4061/2011/327923
work_keys_str_mv AT madhunapantulasubbaraov therapeuticimplicationsoftargetingaktsignalinginmelanoma
AT robertsongavinp therapeuticimplicationsoftargetingaktsignalinginmelanoma