title: Functional genomics lead to new therapies in follicular lymphoma.
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.
authors.affiliation: Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. oriccche@mskcc.org
authors.forename: Elisa
authors.initials: E
authors.lastname: Oricchio
authors.forename: Hans-Guido
authors.initials: HG
authors.lastname: Wendel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6; D016503:Drug Delivery Systems; D023281:Genomics / Q000379:methods; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects* / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D036141:Receptor, EphA7 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D036141:Receptor, EphA7
keywords: genomic data; mouse model; therapies