Synthetic Genetic Targeting of Genome Instability in Cancer

Cancers

Babu V. Sajesh¹  Brent J. Guppy¹ 

[1] Manitoba Institute of Cell Biology, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada;

关键词: cancer;    genome instability;    tumor suppressor gene;    oncogene;    synthetic genetic approach;    synthetic lethality;    synthetic dosage lethality;    cancer therapy;   

DOI  :  10.3390/cancers5030739

来源: mdpi

【 摘 要 】

Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.