JUST IN and via @Merck + @moderna_tx: A landmark moment for cancer immunotherapy. 🎯 Phase 3 INTerpath-001 is positive: the individualized mRNA neoantigen therapy intismeran (V940/mRNA-4157) + pembrolizumab significantly improved both RFS/DMFS vs pembrolizumab alone after resection of high-risk melanoma. For years, the idea of designing a treatment around the unique mutations of each patient’s tumor seemed aspirational. Now we have the first positive Phase 3 trial (N=1137) of an individualized neoantigen therapy—and of an mRNA-based cancer therapy. Personalized cancer vaccines are moving from promise to reality. Now we need to see the magnitude of benefit, durability, and ultimately OS. But today is an important day for the field—and hopefully for our patients. 👏 Congrats to #CathyWu @DanaFarber for her trailblazing research that is materializing in tangible outcomes! At @DanaFarber_GU we are closely working with Cathy + @DFCI_NeoVax team on several GU protocols, after our @Nature work with @BraunMDPhD et al (nature.com/articles/s41586-0…) merck.com/news/merck-and-mod…

August 5 issue of @Nature: 3 foundational papers that substantially expand patient-derived 3D cancer models and show what they can add beyond traditional 2D cell lines. 1️⃣ HCMI: 665 models from 637 patients across 25 cancer types, including rare cancers and more diverse patient populations. Tumor-model genomic concordance was remarkably high (97.8%). Importantly, the work also shows where models can diverge from the original tumor—through stromal loss, clonal selection, and culture-driven epigenetic changes, some of which were reversible. These models are publicly available! 2️⃣ @sangerinstitute : 256 clinically annotated organoids across 5 cancers, with genome-wide CRISPR screens in 162. The screens uncovered dependencies that may be missed in conventional models. A nice example: KRAS dependency in colorectal cancer differed by allele—G12X tumors retained EGFR dependence, whereas Q61H did not. Treatment also reshaped dependencies, highlighting how cancer evolution can create new vulnerabilities. 3️⃣ @broadinstitute DepMap: 314 NextGen models across 10 cancers, including 147 CRISPR screens. These models reproduced tumor lineage far better than traditional cell lines—particularly striking in CNS tumors (93% vs 11%). They also uncovered context-specific dependencies in PDAC and GBM and showed something important: culture conditions themselves can change which genes appear essential (@DanaFarber_GU authors) with @boehmjesse team! Taken together, these studies move cancer dependency mapping closer to the biology of actual human tumors. The model matters—and so does the environment in which we study it. 🔅