title: Oncogenes in cell survival and cell death.
abstract: The transforming effects of proto-oncogenes such as MYC that mediate unrestrained cell proliferation are countered by "intrinsic tumor suppressor mechanisms" that most often trigger apoptosis. Therefore, cooperating genetic or epigenetic effects to suppress apoptosis (e.g., overexpression of BCL2) are required to enable the dual transforming processes of unbridled cell proliferation and robust suppression of apoptosis. Certain oncogenes such as BCR-ABL are capable of concomitantly mediating the inhibition of apoptosis and driving cell proliferation and therefore are less reliant on cooperating lesions for transformation. Accordingly, direct targeting of BCR-ABL through agents such as imatinib have profound antitumor effects. Other oncoproteins such as MYC rely on the anti-apoptotic effects of cooperating oncoproteins such as BCL2 to facilitate tumorigenesis. In these circumstances, where the primary oncogenic driver (e.g., MYC) cannot yet be therapeutically targeted, inhibition of the activity of the cooperating antiapoptotic protein (e.g., BCL2) can be exploited for therapeutic benefit.
authors.affiliation: Cancer Therapeutics Program, Gene Regulation Laboratory, Peter MacCallum Cancer Centre, East Melbourne 3002, Victoria, Australia.
authors.forename: Jake
authors.initials: J
authors.lastname: Shortt
authors.forename: Ricky W
authors.initials: RW
authors.lastname: Johnstone
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D016259:Genes, myc / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D017978:Receptors, Growth Factor