Presented at #ASCO26:
Among patients with previously treated metastatic pancreatic ductal adenocarcinoma, the RAS(ON) inhibitor daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. Full phase 3 RASolute 302 trial results: https://t.co/xwLWBZYRzq
@ASCO
Today in Nature Methods, we propose a bold new vision for biology: Virtual Embryos 🧬🤖
By integrating single-cell and spatial genomics with AI, we can build digital twins of embryogenesis—moving beyond virtual cells to predict cell growth, division, migration, state transitions, and morphogenesis, from genes → cells → organs -> organ systems and whole embryo, in a fully 4D spatiotemporal framework.
Congenital defects affect ~1 in 33 births in the U.S., costing ~$23B annually. This approach could enable truly predictive biology and in silico experimentation to diagnose, prevent, and treat developmental diseases—transforming medicine and improving outcomes for future generations.
If this excites you, come build with us—together with Emily Fox, James Zou (@james_y_zou), and Marinka Zitnik (@marinkazitnik). We also welcome industrial and philanthropic support for this ambitious vision.
Such an interesting paper in @ScienceMagazine from Mien Chie Hung
MTAP deficiency confers resistance to cytosolic nucleic acid sensing and STING agonists
https://t.co/pUHmBXX7CA
If validated, this has relevance to many solid cancers like #PancreaticCancer with MTAP deletions.
New preprint by @mcandrews_kate (previously @KalluriLab, now PI at @MDAndersonNews):
CDK8 remodels the tumor microenvironment to resist the therapeutic efficacy of targeted KRASG12D inhibition in #PancreaticCancer
In this preclinical study, Kate demonstrates that while acute inhibition of KRAS using MRTX1133 leads to infiltration by CD11c+ cells and T-cell infiltration, this window for "immune rejection" is narrow and longer term treatment with KRASi leads to reversal of the immune milieu to one of "immune evasion", orchestrated by tumor cell intrinsic CDK8, which enhances CXCL2-mediated TME remodeling. Targeting CDK8 with a pharmacological strategy, combined with anti-CTLA antibody, reverses this immune milieu back to one of rejection. The translational relevance is obvious since patients are typically on these KRASi longer than most published short term mouse studies. Understanding the immune dynamics over time is important.
Has any CAR-T product ever shown clinical efficacy in pancreatic cancer (besides the occasional transient stable disease).
I am not aware of any such example.
Please correct me if I’m wrong.
Biggest medical discoveries of the week (🧵)
1/8
Treating pre-eclampsia by sprouting new blood vessels
Delivering VEGF to the placenta (intravenously, via placenta-tropic mRNA nanoparticles) resolved high blood pressure and birth weight (in mice!)
https://t.co/NUUUprLUbL
Neuroimmune crosstalk directs T cell differentiation for optimal viral clearance. With our collaborators, we show that neuropeptide CGRP produced by neurons during infection boosts Th1 differentiation while suppressing Th2, via RAMP3 on T cells. @Nature
https://t.co/wofhTDyZcX
Excited to share a new work from @kipnislab by amazing Wenqing Gao (twitter-less) on developing engineered T cell therapy for CNS injury || https://t.co/0BAa3m7J5Q
In @ImmunityCP, Raghu Kalluri discusses the role of extracellular vesicles (EVs) in immune response and immunity. Might EVs be the original primordial units preceding creation of the first cell?
https://t.co/hsSx0VRt3r
Aviv Regev on collaborations: be generous with your ideas, your abilities, with resources that you have, your time, your mindset... And when everyone in a collaboration behaves in this way, then of course, it's a lot of fun.
https://t.co/dyVDQGxKsj @nightsciencepod
A two-in-one drug that modulates neural pathways involved in appetite and reward might prove to be more effective and longer lasting than current weight-loss drugs on the market https://t.co/sJlPYFW5oa
"A structural biologist's dream" is the caption of this Figure 😉
From a beautiful new review of cryo-EM for structural and cell biology @Nature
https://t.co/hnHEdGEEnu
A great scientist is someone who can reinvent themselves continuously. Todd Golub reveals in this episode the secret way the @broadinstitute finds creative people.
https://t.co/8uul8P4AWK
Today we report in @NatureComms the development of laboratory-evolved CBE6 cytosine base editors that offer high on-target C•G-to-T•A editing, virtually no A•T-to-G•C editing, low off-target editing, broad sequence context compatibility, and compatibility with multiple Cas domains.
/1
Prime editing can correct most known disease-causing mutations, and now has a new vehicle to deliver its machinery in mice. The @davidrliu lab has engineered virus-like particles that deliver prime editors efficiently enough to have a therapeutic benefit. https://t.co/FQ5tNd3pta