Why should we still care about oncogenes?
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-alpha treatment produced a sustained cytologic response in approximately 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.
Diehl
Kathleen M
KM
Department of Urology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0940, USA.
Keller
Evan T
ET
Ignatoski
Kathleen M Woods
KM
D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000473:pathology; D009857:Oncogenes / Q000502:physiology*; D000090063:Proto-Oncogene Mas