Improving the efficacy of proteasome inhibitors in the treatment of renal cell carcinoma by combination with the human immunodeficiency virus (HIV)-protease inhibitors lopinavir or nelfinavir.
Dominik AbtAndrej BesseLenka SedlarikovaMarianne KrausJuergen BaderTobias SilzleMartina VodinskaOndrej SlabyHans-Peter SchmidDaniel Stephan EngelerChristoph DriessenLenka BessePublished in: BJU international (2017)
The combination of the proteasome inhibitor carfilzomib and the HIV-PIs lopinavir and nelfinavir has a strong synergistic cytotoxic activity against ccRCCin vitro at therapeutically relevant drug concentrations. This effect is most likely explained by synergistic UPR triggering and ABCB1-modulation caused by HIV-PIs. Our findings suggest that combined treatment of second-generation proteasome inhibitors and HIV-PIs should be investigated in patients with metastatic RCC within a clinical trial.
Keyphrases
- human immunodeficiency virus
- antiretroviral therapy
- hiv infected
- hiv positive
- hepatitis c virus
- hiv testing
- hiv aids
- renal cell carcinoma
- clinical trial
- men who have sex with men
- south africa
- emergency department
- multiple myeloma
- open label
- combination therapy
- mass spectrometry
- drug delivery
- double blind
- single molecule
- anti inflammatory