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PMID: 27197880 Published · ppublish English Journal Article Review

Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

Journal of clinical pharmacology ·Vol. 56 ·No. 12 ·2016-00-00 ·Pages 1484-1499

Schmidt KT, Chau CH, Price DK, Figg WD

Abstract

Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach.

Keywords
molecular targeted therapy next-generation sequencing oncology precision medicine
MeSH Terms
Antineoplastic Agents/therapeutic use Biomarkers, Tumor/metabolism ErbB Receptors/metabolism Humans Medical Oncology/methods,standards Neoplasms/drug therapy,metabolism Precision Medicine/methods,standards Receptor, ErbB-2/metabolism Treatment Outcome
Chemicals
Antineoplastic Agents Biomarkers, Tumor EGFR protein, human ERBB2 protein, human ErbB Receptors Receptor, ErbB-2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Schmidt Keith T
Clinical Pharmacology Program, Office of the Clinical Director, NIH, Bethesda, MD, USA.
Chau Cindy H
Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Price Douglas K
Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Figg William D
Clinical Pharmacology Program, Office of the Clinical Director, NIH, Bethesda, MD, USA. | Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
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Article Info
Journal
Journal of clinical pharmacology
Abbr.
J Clin Pharmacol
ISSN
1552-4604
DOI
10.1002/jcph.765
Published
2016-00-00
Epub
2016-00-17
Pages
1484-1499
Language
English
Region
England
NLM ID
0366372
PMCID
PMC5112148
Subset
IM
Grants
Intramural NIH HHS · Z01 SC006537-15 · United States
Intramural NIH HHS · ZIA BC010627-12 · United States
Intramural NIH HHS · ZIC SC006537-22 · United States
External Links
PubMed source DOI: 10.1002/jcph.765 PMC Full Text View journal details
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