title: Targeting tumor suppressor genes for cancer therapy.
abstract: Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Chemo/Bio Sensing and Chemometrics, College of Biology, Hunan University, Changsha, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Cecil
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Liana
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xiongbin
authors.initials: X
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D023281:Genomics / Q000379:methods; D006801:Humans; D009154:Mutation / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents
keywords: cancer genomics; druggability; gene copy loss; gene therapy; synthetic lethality; target therapy; tumor suppressor