Therapeutic implications of targeting AKT signaling in melanoma

Subbarao V. Madhunapantula, Gavin P. Robertson

Research output: Contribution to journalReview article

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number327923
JournalEnzyme Research
Volume2011
Issue number1
DOIs
StatePublished - Dec 1 2011

Fingerprint

Melanoma
Phosphotransferases
Enzymes
PTEN Phosphohydrolase
Chromosomes, Human, Pair 10
Proto-Oncogene Proteins c-akt
Skin Neoplasms
Protein Transport
Therapeutics
Chromosomes
Phosphatidylinositol 3-Kinases
Drug Resistance
Skin
Research Personnel
Substrates
Pharmaceutical Preparations
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

@article{a4d7f56e923149eaaad63062d96a2e69,
title = "Therapeutic implications of targeting AKT signaling in melanoma",
abstract = "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.",
author = "Madhunapantula, {Subbarao V.} and Robertson, {Gavin P.}",
year = "2011",
month = "12",
day = "1",
doi = "10.4061/2011/327923",
language = "English (US)",
volume = "2011",
journal = "Enzyme Research",
issn = "2090-0406",
publisher = "Hindawi Publishing Corporation",
number = "1",

}

Therapeutic implications of targeting AKT signaling in melanoma. / Madhunapantula, Subbarao V.; Robertson, Gavin P.

In: Enzyme Research, Vol. 2011, No. 1, 327923, 01.12.2011.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Therapeutic implications of targeting AKT signaling in melanoma

AU - Madhunapantula, Subbarao V.

AU - Robertson, Gavin P.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84865849911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865849911&partnerID=8YFLogxK

U2 - 10.4061/2011/327923

DO - 10.4061/2011/327923

M3 - Review article

C2 - 21461351

AN - SCOPUS:84865849911

VL - 2011

JO - Enzyme Research

JF - Enzyme Research

SN - 2090-0406

IS - 1

M1 - 327923

ER -