Managing drug resistance in cancer: lessons from HIV therapy.
Drug resistance is a common cause of treatment failure for HIV infection and cancer. The high mutation rate of HIV leads to genetic heterogeneity among viral populations and provides the seed from which drug-resistant clones emerge in response to therapy. Similarly, most cancers are characterized by extensive genetic, epigenetic, transcriptional and cellular diversity, and drug-resistant cancer cells outgrow their non-resistant peers in a process of somatic evolution. Patient-specific combination of antiviral drugs has emerged as a powerful approach for treating drug-resistant HIV infection, using genotype-based predictions to identify the best matched combination therapy among several hundred possible combinations of HIV drugs. In this Opinion article, we argue that HIV therapy provides a 'blueprint' for designing and validating patient-specific combination therapies in cancer.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. cbock@cemm.oeaw.ac.at
Christoph
C
Bock
Thomas
T
Lengauer
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D024882:Drug Resistance, Viral / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents