Work

Ritonavir and DNA Damage: A New Perspective on an Old Drug

Year: 2025

Type: article

Abstract: Ritonavir (RTV), an effective aspartyl protease inhibitor, was originally developed to counter the replication of human immune deficiency virus and then employed as a pharmacokinetic enhancer in antiretroviral therapy. Yet unexpectedly, RTV exerted antitumor effects that added to its antiviral action, as it impacted the migration, invasion, oxidative stress, and proteasome function of human tumor cells. More recently, RTV was shown to directly inhibit DNA repair enzymes, thereby enhancing radiosensitivity and synergizing with chemotherapeutics across multiple cancer models. However, RTV induced oxidative stress and DNA damage also in non-tumor cells, including the reproductive ones. This duality highlights both the possibility of RTV anticancer use and the concern for its safety. In this Perspective, we propose the repurposing of RTV as a novel tool to potentiate DNA-damage-based antitumor therapies such as radiotherapy and/or chemotherapy. At the same time, we underscore the need for a careful assessment of RTV side effects.

Source: Applied Sciences

DOI: 10.3390/app152212053

Authors: Silvia Pomella, Erika Ferraro, Francesco Marampon, Giovanni Barillari

Institutions: University of Rome Tor Vergata, Bambino Gesù Children's Hospital, Sapienza University of Rome

Language: English

Topic: Cancer therapeutics and mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,896