Nelson Dusetti: TP53 missense–specific transcriptional plasticity drives resistance against cell cycle inhibitors in pancreatic cancer
Nelson Dusetti, Head of the Translational Research and Innovative Therapies Department at the Cancer Research Centre of Marseille (CRCM), shared a post on LinkedIn:
“I’m proud to have contributed to this work, recently published in Science Advances.
“TP53 missense–specific transcriptional plasticity drives resistance against cell cycle inhibitors in pancreatic cancer”
In this study, Shiv K. Singh led an impressive effort exploring how specific TP53 missense mutations, especially R273H/C, shape transcriptional plasticity in pancreatic ductal adenocarcinoma (PDAC). These mutants drive cell cycle progression and define a more aggressive basal-like subtype.
Importantly, their loss reduces tumor growth and metastasis. Yet, targeting them with CDK4/6 inhibitors alone leads to compensatory MAPK/ERK activation, highlighting the need for combined therapeutic approaches.
This study offers crucial insights into how transcriptional plasticity driven by specific TP53 mutations fuels resistance mechanisms, posing major challenges but also revealing new therapeutic opportunities in PDAC. It’s precisely this interplay, between mutation-specific biology, tumor plasticity, and therapeutic vulnerabilities, that underpins our efforts to personalize pancreatic cancer treatment.
I’d like to warmly thank and congratulate Shiv K. Singh for driving this excelent work, and the entire team for the excellent collaboration. It’s been a pleasure contributing to a study that brings us closer to tailored therapies in one of the toughest cancers to treat.”
Title: TP53 missense–specific transcriptional plasticity drives resistance against cell cycle inhibitors in pancreatic cancer
Authors: Laura Urbach, Lena Wieland, Frederike Penz, Rebecca Diya Samuel, Stefan Küffer, Lukas Klein, Christof Lenz, Ulrich Sax, Michael Ghadimi, Ramona Schulz-Heddergott, Elisabeth Hessmann, Volker Ellenrieder, Nelson Dusetti, Shiv K. Singh
Read the Full Article.
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