Article
Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges.
Cancer discovery - 1 Apr 2022
Song Kai, Minami Jenna K, Huang Arthur, Dehkordi Siavash R, Lomeli Shirley H, Luebeck Jens, Goodman Mark H, Moriceau Gatien, Krijgsman Oscar, Dharanipragada Prashanthi, Ridgley Trevor, Crosson William P, Salazar Jesus, Pazol Eli, Karin Gabriel, Jayaraman Rachana, Balanis Nikolas G, Alhani Salwan, Sheu Kyle, Ten Hoeve Johanna, Palermo Amelia, Motika Stephen E, Senaratne T Niroshi, Paraiso Kim H, Hergenrother Paul J, Rao P Nagesh, Multani Asha S, Peeper Daniel S, Bafna Vineet, Lo Roger S, Graeber Thomas G
Abstract excerpt
Focal amplifications (FA) can mediate targeted therapy resistance in cancer. Understanding the structure and dynamics of FAs is critical for designing treatments that overcome plasticity-mediated resistance. We developed a melanoma model of dual MAPK inhibitor (MAPKi) resistance that bears BRAFV600 amplifications through either extrachromosomal DNA (ecDNA)/double minutes (DM) or intrachromosomal homogenously...
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