Rapid identification of therapeutic targets in hematologic malignancies via functional genomics

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

The clinical application of gene-targeted drugs has transformed cancer therapy. The hallmark example of this strategy is use of the ABL kinase inhibitor imatinib for treatment of patients with chronic myeloid leukemia (CML). This remarkable clinical success has also stimulated an expansive search for personalized gene targets in all patients to facilitate broad application of targeted therapy for cancer. However, achievement of this objective will require simultaneous work towards several complementary goals. The first step towards broad application of gene-targeted therapy must entail a rapid means to identify target oncogenes in individual patients. Next, we must identify well-tolerated, gene-specific drugs that are collectively effective against a wide diversity of gene targets. Finally, we must develop protocols by which individual patients are matched with appropriate, gene-targeted drugs in a clinically relevant time frame. While these may seem like difficult tasks, we are fortunate to have a wide variety of new and rapidly evolving research tools at our disposal. These include next-generation sequencing of the genome and transcriptome, single nucleotide polymorphism (SNP)/copy number variations (CNV) and gene expression microarrays, and RNAi libraries for the application of functional screens. In this review we discuss the advantages and disadvantages of each of these techniques with the goal of demonstrating that no single technique will be sufficient as a standalone technology, but rather it will be the integration of all techniques that will enable broad application of gene-targeted cancer therapies.

Original languageEnglish (US)
Pages (from-to)83-93
Number of pages11
JournalTherapeutic Advances in Hematology
Volume2
Issue number2
DOIs
StatePublished - 2011

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Hematologic Neoplasms
Genomics
Genes
Pharmaceutical Preparations
Therapeutics
Neoplasm Genes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
RNA Interference
Oncogenes
Transcriptome
Genetic Therapy
Libraries
Single Nucleotide Polymorphism
Neoplasms
Phosphotransferases
Genome
Technology
Gene Expression
Research

Keywords

  • deep sequencing
  • gene chip
  • neoplasia
  • personalized medicine
  • shRNA screen
  • siRNA screen

ASJC Scopus subject areas

  • Hematology

Cite this

Rapid identification of therapeutic targets in hematologic malignancies via functional genomics. / Tyner, Jeffrey.

In: Therapeutic Advances in Hematology, Vol. 2, No. 2, 2011, p. 83-93.

Research output: Contribution to journalReview article

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