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World J Med Genet. Dec 27, 2011; 1(1): 14-22
Published online Dec 27, 2011. doi: 10.5496/wjmg.v1.i1.14
Genetic interactions in translational research on cancer
Bingliang Fang
Bingliang Fang, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Author contributions: Fang B solely contributed to this paper.
Supported by The National Institutes of Health through MD Anderson’s Cancer Center Support Grant CA016672, which supports the Lung Program; National Cancer Institute grants R01 CA092487 and R01 CA 124951; and a Specialized Program of Research Excellence Grant CA-070907
Correspondence to: Bingliang Fang, MD, PhD, Professor, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. bfang@mdanderson.org
Telephone: +1-713- 5639147 Fax: +1-713-7944901
Received: July 27, 2011
Revised: October 18, 2011
Accepted: December 17, 2011
Published online: December 27, 2011
Abstract

Genetic interactions are functional crosstalk among different genetic loci that lead to phenotypic changes, such as health or viability alterations. A disease or lethal phenotype that results from the combined effects of gene mutations at different loci is termed a synthetic sickness or synthetic lethality, respectively. Studies of genetic interaction have provided insight on the relationships among biochemical processes or pathways. Cancer results from genetic interactions and is a major focus of current studies in genetic interactions. Various basic and translational cancer studies have explored the concept of genetic interactions, including studies of the mechanistic characterization of genes, drug discovery, biomarker identification and the rational design of combination therapies. This review discusses the implications of genetic interactions in the development of personalized cancer therapies, the identification of treatment-responsive genes, the delineation of mechanisms of chemoresistance and the rational design of combined therapeutic strategies to overcome drug resistance.

Keywords: Cancer, Drug discovery, Mutation, Genetic interaction, Target identification, Chemoresistance