Ashok Venkitaraman & colleagues address a fundamental question that has plagued the BRCA field for years - why do individuals with monoallelic germline mutations of BRCA2 still get cancers like #PancreaticCancer , sans a classic “second hit”. Fantastic study tying aberrant

I'm not always convinced that OS is the only appropriate endpoint to support market authorization/demonstrate clinical benefit. Prasad's critique is ofc important to reckon with.

1. ‘target validation using human genetics’, first. 🧬 Great write-up on what to vet for in new medicines!

A loss of function mutation in CLDN25 causing Pelizaeus-Merzbacher-like leukodystrophy
doi.org/10.1093/hmg/dd…

New paper out, for #cerebellum fans. Probing the genetic architecture of cerebellar lobules using the UK Biobank. Very grateful to amaia_cc for her work on this paper. We found new cerebello/cortical correlations + signal linked to introgression ‘deserts’
nature.com/articles/s4159…

Cross-ancestry GWAS of serum urate levels in >1 million individuals. The SNP-based heritability of serum urate in Europeans is 8.7% (East Asians - 11.9%) of which, impressively, ~96% (East Asians - 71%) can be now explained by genome-wide significant SNPs. At least in Europeans,

Broad acting Ras inhibitor that works remarkably well in mouse models of pancreatic cancer developed. This is one of the worst cancers & patients are really keen to enrol in trials.

Question: what limits enrolment? I am reminded of Matthew Herper 's article for STAT where

Exploring the #genomic architecture of circulating #cytokines in the largest to-date dataset of 75,000 individuals, we find

👉169 loci associated with cytokine levels
👉 promising drug targets for immune-mediated diseases

Check out for more:
medrxiv.org/content/10.110…

FDA action on oncology drug applications has stayed high in April. After a slow start to year, March and April has seen a pick up like.

The screenshot below omits the label expansions for ciltacabtagene autoleucel & idecabtagene vicleucel:

Mosaic loss of Y chromosome is more frequent in the 'the European American (EA) ancestry group compared to those of Hispanic American (HA), African American (AA), and East Asian (EAS) ancestry.' based on analysis of ~25k TOPMed genomes.
Jakubek et al. MedRxiv

Phase 1 results of Dato-DXd for pretreated HER2- MBC (N=85) out in JCO. ORR was 26.8% and 31.8% for HR+/HER2- MBC & TNBC. Toxicities: stomatitis (80%), nausea (60%), ocular tox (40%), IRR, ILD. Lower ORR (14.3%) among 14 pts with TNBC and prior topo1-ADC. ascopubs.org/doi/pdf/10.120…

Good move IMHO. I’ve seen academic medical centers use non-compete clauses to limit competition by stifling physician mobility.

U.S. bans noncompete agreements for nearly all jobs. apple.news/AGjJqWH1kRLeha…

So excited to finally share our X chromosome wide association study (XWAS) of Alzheimer's disease (AD)! Simultaneously the largest genetic association study of AD to date (N=1,152,284). Find out more about the top prioritized gene, SLC9A7 (aka NHE7), here: medrxiv.org/content/10.110…

“Full time” college students spend less than three hours per day in class or doing homework.

A downstream consequence of the marketization of higher education — the customers are getting what they want and what they want is easy classes.

slowboring.com/p/college-stud…

I am fascinated by the finances of the publishing industry, because it's like Hollywood but even more screwed up somehow. elysian.press/p/no-one-buys-…

I can never manage to post here without committing some sort of typo.

FDA grants accelerated approval to tovorafenib for patient with relapsed or refractory BRAF-altered pediatric low-grade glioma fda.gov/drugs/resource…

Join us Thursday at 12 pm ET for a webinar with MEDITECH’s Manager of Clinical Product Management, @Jennifer Ford, & GenomOncology’s VP, James Cole. Learn how we're reshaping precision medicine through collaboration. Register now! genomoncology.zoom.us/webinar/regist…

#PrecisionMedicine

In UK Biobank, individuals who had high polygenic score for educational attainment but performed poorly in fluid intelligence test and/or had poor education ('deviators') were more likely to carry neurodevelopmental disorder-related rare variants. Great demonstration of liability