Targeting loss-of-function mutations in tumor-suppressor genes as a strategy for development of cancer therapeutic agents.
Two types of genetic mutations, gain-of-function in oncogenes and loss-of-function in tumor-suppressor genes, are important molecular bases of tumorigenesis of human cancers. Target-based drug discovery is the main stream of contemporary cancer therapeutic development but largely focuses on gain-of-function mutations in oncogenes. Loss-of-function mutations in tumor-suppressor genes are often neglected as therapeutic targets. In this review, we discuss the feasibility of targeting loss-of-function mutations in tumor-suppressor genes for the identification of cancer-specific therapeutic agents.
Wang
Hong
H
The Translational Genomics Research Institute, Translational Drug Development Division, Phoenix, AZ 85004, USA. hwang@tgen.org
Han
Haiyong
H
Mousses
Spyro
S
Von Hoff
Daniel D
DD
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy*; D012329:RNA, Bacterial / Q000235:genetics
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; C042027:RNA I; D012329:RNA, Bacterial