Impact of viral oncogenesis on responses to anti-cancer drugs and irradiation.
The view that chemical or physical oncogenesis and tumor therapy resistance represent different parts of common cellular alterations gained considerable attractiveness, because it explains the inherent unreponsiveness of many tumors. Viruses are potent oncogenes and are causally linked to approximately one-fifth of all human malignancies. Whether viral oncogenesis exerts comparable effects was less clear. Recent progress in experimental research provided ample evidence that viruses affect response of tumor cells toward anti-cancer drugs and irradiation. Resistance to cytostatic drugs and radiation develops by alterations at the drug-target sites (i.e., DNA or specific target proteins), upstream (i.e., detoxification mechanisms), or downstream of them (i.e., programmed cell death). Viruses interfere with specific cellular genes at these three levels. Viral proteins induce the expression and expression of drug resistance genes, that is, MDR1, DHFR, or CAD. Viral interactions with the tumor suppressor genes (p53, pRB) abrogate cell cycle arrests and disturb DNA repair of drug- and radiation-induced DNA lesions. The readiness to commit cellular suicide (apoptosis) is also affected by viral genes. The connection between viral oncogenesis and the response of tumor cells to treatment adds a new dimension to tumor biology and may have important consequences for oncological treatment modalities in the future.
Efferth
T
T
Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Erlangen, Germany.
Grassmann
R
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D016158:Genes, p53 / Q000187:drug effects / Q000502:physiology; D015613:Hepadnaviridae / Q000187:drug effects / Q000378:metabolism; D006564:Herpesviridae / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D027383:Papillomaviridae / Q000187:drug effects / Q000378:metabolism; D027382:Polyomaviridae; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014412:Tumor Virus Infections / Q000150:complications*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents