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Sci Rep2025;15(1):3048.January 24, 2025Journal Article

Transposon mediated functional genomic screening for BRAF inhibitor resistance reveals convergent Hippo and MAPK pathway activation events.

Li Chen1, Iulian Pruteanu-Malinici2,3, Anahita Dastur2,4, Xunqin Yin2,5, Dennie Frederick2,5, Ruslan I Sadreyev6, Cyril H Benes2,7
1Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA. lichenboston@gmail.com.
2Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
3Flagship Pioneering, Cambridge, MA, USA.
4Sonata Therapeutics, Watertown, MA, USA.
5Broad Institute, Cambridge, MA, USA.
6Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02115, USA.
7Treeline Biosciences, San Diego, CA, USA.
PubMed PMC DOI PDF

Abstract

Genotype-informed anticancer therapies such as BRAF inhibitors can show remarkable clinical efficacy in BRAF-mutant melanoma; however, drug resistance poses a major hurdle to successful cancer treatment. Many resistance events to targeted therapies have been identified, suggesting a complex path to improve therapeutics. Here, we showed the utility of a piggyBac transposon activation mutagenesis sc…

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