🧬🎯Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study 1/4 @myESMO @ESMO_Open @OncoAlert #bcsm esmoopen.com/article/S2059-… 
Lurbinectedin has antitumor activity against homologous recombination repair-deficient (HRD) cell lines. The mechanism involves irreversible stalling of elongating RNA polymerase II (Pol II) on DNA template and its specific degradation by the ubiquitin/proteasome machinery 2/4
Subsequently, recruitment of DNA repair factors including xeroderma pigmentosum complementation group F nuclease induces the accumulation of double-strand breaks and apoptosis as downstream events. These effects are increased in HRD cells 3/4
In fact, in BRCA2-mutated cells, this could be related to the concurrence of deficient DNA repair and formation of R-loops that occurs during the elongation step of transcription by RNA polymerase II 4/4
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