Secondary resistance to anti-EGFR therapy by transcriptional reprogramming in patient-derived colorectal cancer models.
Deepak VangalaSwetlana LadiganSven T LiffersSoha NoseirAbdelouahid MaghnoujTina-Maria GötzeBerlinda VerdoodtSusanne Klein-ScoryLaura GodfreyMartina K ZowadaMario HuertaDaniel L EdelsteinJaime Martinez de VillarrealMiriam MarquésJörg KumbrinkAndreas JungTobias SchiergensJens WernerVolker HeinemannSebastian StintzingDoris LindoerferUlrich MansmannMichael PohlChristian TeschendorfChristiane BernhardtHeiner WoltersJosef SternSelami UstaRichard ViebahnJacob AdmardNicolas CasadeiStefan FröhlingClaudia R BallJens T SivekeHanno GlimmAndrea TannapfelWolff SchmiegelStephan A HahnPublished in: Genome medicine (2021)
Our study demonstrates that SR PDX tumors provide a unique platform to study molecular SR mechanisms and allow testing of multiple treatments for efficient targeting of SR mechanisms, not possible in the patient. Importantly, it suggests that the development of anti-EGFR tolerant cells via transcriptional reprogramming as a cause of anti-EGFR SR in CRC is likely more prevalent than previously anticipated. It emphasizes the need for analyses of SR tumor tissues at a multi-omics level for a comprehensive molecular understanding of anti-EGFR SR in CRC.