RNA interference technologies and their use in cancer research.
OBJECTIVE
Recently, RNA interference has evolved into a powerful research tool to functionally characterize genes. Genome-wide RNA interference reagents can study the loss-of-function phenotypes of candidate genes in the context of various disease model systems. In this review, we discuss the data from the most recent studies using RNA interference reagents with a focus on RNA interference-based genomic screening as a tool to expand our knowledge about the molecular basis of cancer.


RESULTS
Tumorigenesis is the result of the progressive accumulation of mutations in genes controlling cell proliferation and death. Various genes carrying these alterations are known to be directly linked to tumor growth; however, how to translate this knowledge into effective chemotherapeutics, nontoxic to normal cells, is still a subject of intensive research.


CONCLUSIONS
Loss-of-function studies offer a potential for validation of known and unrecognized tumor-associated targets. RNA interference-mediated gene knockdown can be exploited to study the reprogrammed circuitry of genes, discover gene interactions restricted to cancer cells and identify mechanisms of chemoresistance in cancer cells. In addition, the simultaneous use of cancer drugs and RNA interference also provides a paradigm to develop strategies to inactivate essential genes promoting neoplastic growth.
Gaither
Alex
A
Genome and Proteome Sciences Department, Platform and Chemical Biology Unit, Novartis Institute for Biomedical Research, Cambridge, Massachusetts 02139, USA.
Iourgenko
Vadim
V
D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology*
D009363:Neoplasm Proteins