Recent developments in prognostic and predictive testing in uveal melanoma

Matthew G. Field, J. William Harbour

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: To provide an update on the rapidly evolving methods for assessing prognosis and predicting response to targeted molecular therapy in uveal melanoma. RECENT FINDINGS: The techniques for assessing prognosis in uveal melanoma have evolved from simple physical features, such as tumor size, location, and cell morphology, to the slightly more sophisticated counting of chromosomal gains and losses. More recently, gene expression profiling has provided a highly accurate and biologically informative gold standard for molecular prognostication. The latest step in the evolution of molecular testing has been the recent discovery of major driver mutations that allow predictive testing of response to targeted molecular therapies. Mutations in GNAQ and GNA11 are early events that promote cell proliferation, and these mutations are sensitive to MAPK kinase, PKC, and AKT inhibitors. Mutations in BAP1, SF3B1, and EIF1AX are later events that are largely mutually exclusive. Mutations in BAP1 are strongly associated with metastasis, whereas those in SF3B1 and EIF1AX are associated with good prognosis. Uveal melanomas with BAP1 mutations demonstrate sensitivity to epigenetic modulators, such as histone deacetylase inhibitors. Clinical trials are now available to evaluate the efficacy of these targeted molecular agents in patients with uveal melanoma. SUMMARY: Molecular prognostic testing and enrollment of high-risk patients into clinical trials of targeted molecular therapy are rapidly becoming the standard of care in the management of uveal melanoma.

Original languageEnglish
Pages (from-to)234-239
Number of pages6
JournalCurrent Opinion in Ophthalmology
Volume25
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Molecular Targeted Therapy
Mutation
Clinical Trials
Histone Deacetylase Inhibitors
Molecular Evolution
Mitogen-Activated Protein Kinase Kinases
Gene Expression Profiling
Proxy
Standard of Care
Cell Size
Epigenomics
Uveal melanoma
Cell Proliferation
Neoplasm Metastasis
Neoplasms

Keywords

  • BAP1
  • gene expression profiling
  • metastasis
  • prognosis
  • uveal melanoma

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Recent developments in prognostic and predictive testing in uveal melanoma. / Field, Matthew G.; William Harbour, J.

In: Current Opinion in Ophthalmology, Vol. 25, No. 3, 01.01.2014, p. 234-239.

Research output: Contribution to journalArticle

@article{df2a753194c8453fa78bbdbfd50a9188,
title = "Recent developments in prognostic and predictive testing in uveal melanoma",
abstract = "PURPOSE OF REVIEW: To provide an update on the rapidly evolving methods for assessing prognosis and predicting response to targeted molecular therapy in uveal melanoma. RECENT FINDINGS: The techniques for assessing prognosis in uveal melanoma have evolved from simple physical features, such as tumor size, location, and cell morphology, to the slightly more sophisticated counting of chromosomal gains and losses. More recently, gene expression profiling has provided a highly accurate and biologically informative gold standard for molecular prognostication. The latest step in the evolution of molecular testing has been the recent discovery of major driver mutations that allow predictive testing of response to targeted molecular therapies. Mutations in GNAQ and GNA11 are early events that promote cell proliferation, and these mutations are sensitive to MAPK kinase, PKC, and AKT inhibitors. Mutations in BAP1, SF3B1, and EIF1AX are later events that are largely mutually exclusive. Mutations in BAP1 are strongly associated with metastasis, whereas those in SF3B1 and EIF1AX are associated with good prognosis. Uveal melanomas with BAP1 mutations demonstrate sensitivity to epigenetic modulators, such as histone deacetylase inhibitors. Clinical trials are now available to evaluate the efficacy of these targeted molecular agents in patients with uveal melanoma. SUMMARY: Molecular prognostic testing and enrollment of high-risk patients into clinical trials of targeted molecular therapy are rapidly becoming the standard of care in the management of uveal melanoma.",
keywords = "BAP1, gene expression profiling, metastasis, prognosis, uveal melanoma",
author = "Field, {Matthew G.} and {William Harbour}, J.",
year = "2014",
month = "1",
day = "1",
doi = "10.1097/ICU.0000000000000051",
language = "English",
volume = "25",
pages = "234--239",
journal = "Current Opinion in Ophthalmology",
issn = "1040-8738",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Recent developments in prognostic and predictive testing in uveal melanoma

AU - Field, Matthew G.

AU - William Harbour, J.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - PURPOSE OF REVIEW: To provide an update on the rapidly evolving methods for assessing prognosis and predicting response to targeted molecular therapy in uveal melanoma. RECENT FINDINGS: The techniques for assessing prognosis in uveal melanoma have evolved from simple physical features, such as tumor size, location, and cell morphology, to the slightly more sophisticated counting of chromosomal gains and losses. More recently, gene expression profiling has provided a highly accurate and biologically informative gold standard for molecular prognostication. The latest step in the evolution of molecular testing has been the recent discovery of major driver mutations that allow predictive testing of response to targeted molecular therapies. Mutations in GNAQ and GNA11 are early events that promote cell proliferation, and these mutations are sensitive to MAPK kinase, PKC, and AKT inhibitors. Mutations in BAP1, SF3B1, and EIF1AX are later events that are largely mutually exclusive. Mutations in BAP1 are strongly associated with metastasis, whereas those in SF3B1 and EIF1AX are associated with good prognosis. Uveal melanomas with BAP1 mutations demonstrate sensitivity to epigenetic modulators, such as histone deacetylase inhibitors. Clinical trials are now available to evaluate the efficacy of these targeted molecular agents in patients with uveal melanoma. SUMMARY: Molecular prognostic testing and enrollment of high-risk patients into clinical trials of targeted molecular therapy are rapidly becoming the standard of care in the management of uveal melanoma.

AB - PURPOSE OF REVIEW: To provide an update on the rapidly evolving methods for assessing prognosis and predicting response to targeted molecular therapy in uveal melanoma. RECENT FINDINGS: The techniques for assessing prognosis in uveal melanoma have evolved from simple physical features, such as tumor size, location, and cell morphology, to the slightly more sophisticated counting of chromosomal gains and losses. More recently, gene expression profiling has provided a highly accurate and biologically informative gold standard for molecular prognostication. The latest step in the evolution of molecular testing has been the recent discovery of major driver mutations that allow predictive testing of response to targeted molecular therapies. Mutations in GNAQ and GNA11 are early events that promote cell proliferation, and these mutations are sensitive to MAPK kinase, PKC, and AKT inhibitors. Mutations in BAP1, SF3B1, and EIF1AX are later events that are largely mutually exclusive. Mutations in BAP1 are strongly associated with metastasis, whereas those in SF3B1 and EIF1AX are associated with good prognosis. Uveal melanomas with BAP1 mutations demonstrate sensitivity to epigenetic modulators, such as histone deacetylase inhibitors. Clinical trials are now available to evaluate the efficacy of these targeted molecular agents in patients with uveal melanoma. SUMMARY: Molecular prognostic testing and enrollment of high-risk patients into clinical trials of targeted molecular therapy are rapidly becoming the standard of care in the management of uveal melanoma.

KW - BAP1

KW - gene expression profiling

KW - metastasis

KW - prognosis

KW - uveal melanoma

UR - http://www.scopus.com/inward/record.url?scp=84898031553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898031553&partnerID=8YFLogxK

U2 - 10.1097/ICU.0000000000000051

DO - 10.1097/ICU.0000000000000051

M3 - Article

C2 - 24713608

AN - SCOPUS:84898031553

VL - 25

SP - 234

EP - 239

JO - Current Opinion in Ophthalmology

JF - Current Opinion in Ophthalmology

SN - 1040-8738

IS - 3

ER -