Approaches to repurposing reverse transcriptase antivirals in cancer.

Area of Science:

• Molecular Biology
• Virology
• Oncology

Background:

• Cellular regulation involves non-terminal repeat retrotransposons and endogenous retroviruses.
• Reverse transcriptase (RT) plays a key role in these processes.
• RT inhibitors (RTIs) are explored for their potential in cancer therapy.

Purpose of the Study:

• To review the role of RT inhibition in cellular regulation.
• To discuss RT inhibitors (RTIs) as potential anticancer agents.
• To explore the mechanisms by which RTIs induce cytotoxicity in cancer cells.

Main Methods:

• Review of existing literature on RT inhibitors and their effects on cancer cells.
• Analysis of the mechanisms of cytotoxicity induced by nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs).
• Investigation into the role of LINE-1 elements and the cGAS-STING pathway in RTI-mediated effects.

Main Results:

• RTIs, including NRTIs and NNRTIs, exhibit cytotoxicity in cancer cells, likely via endogenous RT inhibition.
• RTIs induce cell cycle arrest and suppress transposable elements, notably inhibiting LINE-1.
• LINE-1-derived DNA can activate the cGAS-STING pathway, promoting cell cycle arrest and immune responses.

Conclusions:

• RTIs induce DNA strand breaks, incomplete retrotransposition, cell cycle arrest, and immune responses in cancer cells.
• The relationship between PARP1, PARP2, DNA methylation, and LINE-1 retrotransposition warrants further investigation.
• RT inhibitors like efavirenz show promise for preclinical evaluation as repurposed cancer drugs.