LAUSR

Significance The role of endogenous retrotransposons in cancer initiation and progression has been traditionally viewed in the context of their mutagenic activity. The main conclusion of the present work is that retrotransposons can stimulate treatment resistance by the induction of prosurvival inflammatory pathways, a mechanism that is distinct from retrotransposon-mediated mutagenesis. Furthermore, this mechanism is “druggable”, evidenced by partial reversion via reverse transcriptase inhibitors. In this regard, drugs targeting L1-expressing cells represent a category of anticancer agents that lack direct antitumor activity but are capable of suppressing tumor adaptability. This type of pharmaceutical is projected to improve the outcome of any anticancer treatment by extending progression-free survival following initial response.