Functional genomics lead to new therapies in follicular lymphoma

Ann N Y Acad Sci. 2013 Jul:1293:18-24. doi: 10.1111/nyas.12120. Epub 2013 May 15.

Abstract

Recent technological advances allow analysis of genomic changes in cancer in unprecedented detail. The next challenge is to prioritize the multitude of genetic aberrations found and identify therapeutic opportunities. We recently completed a study that illustrates the use of unbiased genetic screens and murine cancer models to find therapeutic targets among complex genomic data. We genetically dissected the common deletion of chromosome 6q and identified the ephrin receptor A7 (EPHA7) as a tumor suppressor in lymphoma. Notably, EPHA7 encodes a soluble splice variant that acts as an extrinsic tumor suppressor. Accordingly, we developed an antibody-based strategy to specifically deliver EPHA7 back to tumors that have lost this gene. Recent sequencing studies have implicated EPHA7 in lung cancer and other tumors, suggesting a broader therapeutic potential for antibody-mediated delivery of this tumor suppressor for cancer therapy. Together, our comprehensive approach provides new insights into cancer biology and may directly lead to the development of new cancer therapies.

Keywords: genomic data; mouse model; therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 6
  • Drug Delivery Systems*
  • Genomics / methods
  • Humans
  • Lymph Nodes / drug effects*
  • Lymph Nodes / metabolism
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / metabolism
  • Mutation
  • Neoplasm Proteins / administration & dosage
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / therapeutic use*
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Protein Isoforms / administration & dosage
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Isoforms / therapeutic use
  • Receptor, EphA7 / administration & dosage
  • Receptor, EphA7 / genetics
  • Receptor, EphA7 / metabolism
  • Receptor, EphA7 / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Neoplasm Proteins
  • Protein Isoforms
  • Receptor, EphA7