2023
E7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial
Bewersdorf J, Stahl M, Taylor J, Mi X, Chandhok N, Watts J, Derkach A, Wysocki M, Lu S, Bourcier J, Hogg S, Rahman J, Chaudhry S, Totiger T, Abdel-Wahab O, Stein E. E7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial. Leukemia 2023, 37: 2512-2516. PMID: 37814121, PMCID: PMC10681888, DOI: 10.1038/s41375-023-02050-4.Peer-Reviewed Original ResearchWhy do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS
Frumm S, Shimony S, Stone R, DeAngelo D, Bewersdorf J, Zeidan A, Stahl M. Why do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS. Blood Reviews 2023, 60: 101056. PMID: 36805300, DOI: 10.1016/j.blre.2023.101056.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeDNA methyltransferase inhibitorLow risk (LR) MDSHigh-risk myelodysplastic syndromeHigh transfusion needsRisk myelodysplastic syndromesCurrent treatment landscapeErythropoiesis-stimulating agentsNovel drug developmentHR-MDSTreatment landscapeTransfusion needsTargetable mutationsClinical trialsMDS pathogenesisNew agentsRing sideroblastsMore drugsUnmet needTherapy developmentDrug developmentMethyltransferase inhibitorFactor mutationsApprovalInflammation
2022
Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells
North K, Benbarche S, Liu B, Pangallo J, Chen S, Stahl M, Bewersdorf J, Stanley R, Erickson C, Cho H, Pineda J, Thomas J, Polaski J, Belleville A, Gabel A, Udy D, Humbert O, Kiem H, Abdel-Wahab O, Bradley R. Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells. Nature Biotechnology 2022, 40: 1103-1113. PMID: 35241838, PMCID: PMC9288984, DOI: 10.1038/s41587-022-01224-2.Peer-Reviewed Original ResearchConceptsBreast cancerExpression of herpes simplex virus thymidine kinaseHerpes simplex virus thymidine kinaseCancer cellsPancreatic cancer cells in vitroWild-type cellsCancer cells in vitroCancer gene therapyTargeting of cancer cellsTumor-specific changesUveal melanoma cellsTreatment in vivoSynthetic intronChange-of-function mutationsCells in vitroUveal melanomaSF3B1 mutationsHSV-tkGene therapyTumor cellsIsogenic wild-type cellsMelanoma cellsRNA splicing factorsCancerHost survival