Mining the cancer genome uncovers therapeutic activity of EphA7 against lymphoma

Cell Cycle. 2012 Mar 15;11(6):1076-80. doi: 10.4161/cc.11.6.19451. Epub 2012 Mar 15.

Abstract

The functional annotation of the cancer genome can reveal new opportunities for cancer therapies. The wealth of genomic data on various cancers has not yet been mined for clinically and therapeutically useful information. We use cross-comparisons of genomic data with the results of unbiased genetic screens to prioritize genomic changes for further study. In this manner, we have identified a soluble variant of the ephrin receptor A7 (EPHA7 (TR) ) as a tumor suppressor that is lost in lymphoma. We also developed antibody-based delivery to restore this tumor suppressor to the cancer cells in situ. We will discuss our strategy of screening genomic data, specific findings concerning EPHA7 and the potential for future discoveries.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / metabolism
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antigens, CD20 / metabolism
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Data Mining*
  • Databases, Genetic
  • Drug Delivery Systems / methods
  • Genetic Testing
  • Genome, Human*
  • Humans
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / therapy*
  • MAP Kinase Signaling System
  • Mice
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Interference
  • Receptor, EphA7 / genetics
  • Receptor, EphA7 / metabolism*
  • Receptor, EphA7 / therapeutic use
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Recombinant Fusion Proteins / therapeutic use
  • Rituximab
  • Solubility
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antineoplastic Agents
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Tumor Suppressor Proteins
  • Rituximab
  • Receptor, EphA7