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Reviews

Why should we still care about oncogenes?

Departments of ¹ Urology and ² Surgery, University of Michigan Health Systems, Ann Arbor, Michigan

Requests for reprints: Kathleen M. Woods Ignatoski, Radiation Oncology, University of Michigan, 5111 CCGC, Room 7111 CCGC, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0940. Phone: 734-615-3818; Fax: 734-647-9480. E-mail: kwi{at}umich.edu

Although oncogenes and their transformation mechanisms have been known for 30 years, we are just now using our understanding of protein function to abrogate the activity of these genes to block cancer growth. The advent of specific small-molecule inhibitors has been a tremendous step in the fight against cancer and their main targets are the cellular counterparts of viral oncogenes. The best-known example of a molecular therapeutic is Gleevec (imatinib). In the early 1990s, IFN- treatment produced a sustained cytologic response in 33% of chronic myelogenous leukemia patients. Today, with Gleevec targeting the kinase activity of the proto-oncogene abl, the hematologic response rate in chronic myelogenous leukemia patients is 95% with 89% progression-free survival at 18 months. There are still drawbacks to the new therapies, such as drug resistance after a period of treatment, but the drawbacks are being studied experimentally. New drugs and combination therapies are being designed that will bypass the resistance mechanisms. [Mol Cancer Ther 2007;6(2):418–27]

³ Traditional nomenclature is used in this review. Viral oncogenes will be designated as v-onc. Proto-oncogenes, or cellular homologues to viral oncogenes, will be designated as c-onc. Proteins will be designated as the gene name starting with a capital letter. The term "oncogene" is sometimes used to describe a cellular gene that has been shown to play a role in tumorigenesis.

⁴ K.M. Diehl, N.K. Grewal, S.P. Ethier, K.M.W. Ignatoski. p38MAPK-activated AKT in HER-2-over expressing human breast cancer cells acts as an EGF-independent survival signal, J Surg Res, in press.

⁵ http://www.clinicaltrials.gov/

Received 9/29/06; revised 11/13/06; accepted 12/ 6/06.