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<p>The synergy between SWI/SNF and Polycomb Repressive Complexes (PRCs) has been a topic of extensive research. The demonstrated heightened preclinical sensitivity of SWI/SNF gene mutations to EZH2 inhibition together with the accelerated approval of Tazemetostat for selected EZH2 mutant tumors by the FDA, has significantly expanded our understanding of chromatin remodeling complexes and their vulnerabilities. Here we report a durable response in a patient with PBRM1 mutated cholangiocarcinoma treated with Tazemetostat. We provide hypothesis-generating mechanistic findings into the relationship between PBRM1 mutations and EZH2 inhibition and the interplay between the SWI/SNF and PRC2 complexes.</p>

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Prolonged survival in a patient with pbrm1 mutated metastatic cholangiocarcinoma receiving tazemetostat

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月24日

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  • Manuel Pedregal,
  • Esther Cabañas Morafraile,
  • Alberto Garrido,
  • Bernard Doger,
  • Tatiana Hernandez,
  • Daniel Morillo,
  • Balázs Győrffy,
  • Alberto Ocaña,
  • Pablo Minguez,
  • Victor Moreno

摘要

The synergy between SWI/SNF and Polycomb Repressive Complexes (PRCs) has been a topic of extensive research. The demonstrated heightened preclinical sensitivity of SWI/SNF gene mutations to EZH2 inhibition together with the accelerated approval of Tazemetostat for selected EZH2 mutant tumors by the FDA, has significantly expanded our understanding of chromatin remodeling complexes and their vulnerabilities. Here we report a durable response in a patient with PBRM1 mutated cholangiocarcinoma treated with Tazemetostat. We provide hypothesis-generating mechanistic findings into the relationship between PBRM1 mutations and EZH2 inhibition and the interplay between the SWI/SNF and PRC2 complexes.