The human immunodeficiency virus protease inhibitor ritonavir is potentially active against urological malignancies

Area of Science:

• Oncology
• Pharmacology
• Drug Repositioning

Background:

• Ritonavir, an HIV protease inhibitor, exhibits antineoplastic properties.
• Its mechanism involves inhibiting key cancer cell signaling pathways like Akt and nuclear factor-kappaB.
• Ritonavir increases cellular unfolded proteins by inhibiting proteasome and heat shock protein 90.

Purpose of the Study:

• To investigate the antineoplastic activity of ritonavir for potential use in urological malignancies.
• To explore drug repositioning strategies for ritonavir in cancer therapy.
• To elucidate the mechanisms underlying ritonavir's anti-cancer effects.

Main Methods:

• Investigating ritonavir's effects on Akt and nuclear factor-kappaB signaling pathways.
• Analyzing ritonavir's impact on cellular unfolded protein levels via proteasome and HSP90 inhibition.
• Evaluating ritonavir's role as a cytochrome P450 3A4 and P-glycoprotein inhibitor.
• Assessing ritonavir's immunomodulatory effects.

Main Results:

• Ritonavir effectively inhibits cancer cell signaling pathways.
• It induces endoplasmic reticulum stress, leading to cancer cell death, especially when combined with other agents.
• Ritonavir enhances the efficacy of co-administered drugs by increasing their intracellular concentrations.
• Ritonavir demonstrates immunomodulatory activity relevant to cancer treatment.

Conclusions:

• Ritonavir's multifaceted mechanisms offer a novel approach to cancer treatment.
• It holds potential for treating drug-refractory urological malignancies and other cancers.
• Drug repositioning of ritonavir presents a promising therapeutic strategy.