2023
Protein degraders enter the clinic — a new approach to cancer therapy
Chirnomas D, Hornberger K, Crews C. Protein degraders enter the clinic — a new approach to cancer therapy. Nature Reviews Clinical Oncology 2023, 20: 265-278. PMID: 36781982, DOI: 10.1038/s41571-023-00736-3.Peer-Reviewed Original ResearchConceptsPhase III trialsCancer therapyNovel therapeutic modalitiesIII trialsClinical trialsPreclinical modelsClinical studiesTherapeutic modalitiesPharmacokinetic dataSmall molecule inhibitorsDisease pathogenesisClinical testingTumor typesDrug concentrationsPreclinical researchCancer treatmentPhase IFirst safetyUbiquitin-proteasome systemPatientsProtein degradersTherapyMore evidenceTrialsRigorous evaluation
2021
Mutant-selective degradation by BRAF-targeting PROTACs
Alabi S, Jaime-Figueroa S, Yao Z, Gao Y, Hines J, Samarasinghe KTG, Vogt L, Rosen N, Crews CM. Mutant-selective degradation by BRAF-targeting PROTACs. Nature Communications 2021, 12: 920. PMID: 33568647, PMCID: PMC7876048, DOI: 10.1038/s41467-021-21159-7.Peer-Reviewed Original ResearchConceptsInhibitor-based therapyBRAF inhibitor-based therapiesBRAF missense mutationsCancer cell growthBRAF V600Current treatmentNew therapiesTherapeutic windowXenograft modelBRAF mutantMutant BRAFVivo efficacyDrug modalitiesRaf family membersProteolysis targeting chimera (PROTAC) technologyTherapyBRAFMissense mutationsFamily membersBRAFWTCell growthDegree of selectivityInactivated conformationPatientsV600