Our latest - introducing the Molecular Oncology Almanac (MOAlmanac): paired clinical interpretation algorithm + knowledge base for precision cancer medicine @moalmanac
Congrats @brendan_reardon et al! @DanaFarber @broadinstitute nature.com/articles/s4301… @NatureCancer [1/12] (Plus shout outs to @natemoore and @NickMoore [no relation] who contributed greatly to this effort during their research time in med school. The co-authors, reviewers, editors, and those mentioned in acknowledgements were instrumental to both this resource and study)

Here's our latest, a deep molecular dive into exceptional responders to anti-androgen therapy before surgery - congrats @aloktewar @alexorscanner Dr. Taplin @DanaFarber_GU et al!

cell.com/cell-reports/f… @CellReports

[1/n] (See also co-published/co-submitted wonderful story by @Chris_Barbieri1 lab with convergent science! cell.com/cell-reports/f…)

Here’s our latest, a deep dive into fusions and partner or "collateral" cancer dependencies

Interesting findings for pediatric and adult cancers...

Congrats Dr. Riaz Gillani @BostonChildrens @DanaFarber @broadinstitute et al! @CR_AACR @AACR cancerres.aacrjournals.org/content/early/… [1/n] Gene fusions can be important for cancer development, and prior work nicely demonstrated how such events can directly affect the expression or functionality of partner genes in cell line data, e.g.: nature.com/articles/s4146…

Interested to see how the forthcoming data behind the ‘TMB > 10 in all cancer types’ approval addresses a few key issues, having spent a long time thinking about this general topic - some thoughts to follow:

[1/n] (Heeding wise words of @tmprowell - this is *not intended as critique*, but rather some open thoughts on the matter that I'm excited to see in the final data once available - feedback welcome!

https://twitter.com/tmprowell/status/1273043390716948483

)

A brief thread on our latest study, as well as a more general chat on biology & biomarkers for cancer immunogenomics - w/ longtime friend Dirk Schadendorf + rockstar jr faculty @dliu_ccb + more friends! @NatureMedicine @DanaFarber @broadinstitute
nature.com/articles/s4159… [1/n] Many current biology & biomarkers blurry lines in cancer immunogenomics - e.g. our TMB melanoma work:

2014-15: Correlation btwn TMB + clinical benefit to ICB in melanoma → neoantigen biology

Though our 2015 data (ncbi.nlm.nih.gov/pubmed/26359337) suggested weak predictive effect...

Here, we partnered w/ cancer patients + friends @KDeutsch @adamhayden @CultPerfectMoms @CurrentIncurSci @stephanie_mul to liberate their cancer genomic data from clinical labs.

It was a struggle…

...but there’s hope & we have a plan! [1/n] @OSFramework osf.io/gupvq (Updated my bio to have a disclosures link, including consulting for genomics labs which is relevant for this effort. Also pasting here: goo.gl/6kfq2E)

A thread on our latest look at cancer genomics + immune checkpoint blockade → congrats @diana_miao, Claire, @NIVokes et al!

Thx @SU2C @BroadIgnite @HHMINEWS @theNCI for supporting this & the ppl doing it @NatureGenet @DanaFarber @broadinstitute

rdcu.be/5iVz [1/n] We analyzed every tumor-normal exome from patients getting immune checkpoint blockade (ICB) we could get & integrated w/ clinical outcomes for biological and clinical exploration → lots of technical pain here + open questions re: defining clinical benefit

Lots of discussion whether broad cancer NGS testing is good/bad given @JAMAOnc article below. Tbh I'm far more interested in some general issues it exposes re: prospectively testing the precision oncology hypothesis:

jamanetwork.com/journals/jama/… [1/4] 1) NGS testing w/o companion (early phase?) clinical trial network & mid-trial adjustments for when new approvals arise creates a ‘last mile’ problem that reduces potential impact. Can a precision oncology trial have experimental Rx access and be changed in real time? [2/4]

Reflecting on the recent/heated “hype vs. hope” precision oncology debates: It’s not “vs.” → real hope it engenders & current limitations are simultaneously true. This tension mirrors so much of oncology, as @Bob_Wachter elegantly points out here:
nytimes.com/2018/04/19/opi… [1/n] Thankfully, @DHymanMD captured this critical point clearly, here:

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A twitter explainer for our latest #teamscience study rdcu.be/KwgV congrats Josh @stephanie_mul @dliu_ccb @nikolausschultz Arul @CharlesSawyers et al @PCFnews @SU2C @DanaFarber @broadinstitute @MSKCC_OncoNotes @NatureGenet [1/n] I've been lucky to grow up academically around many #prostatecancer scientific 'big machers' & helped with early cancer genomic maps over the last 5+ years, e.g.:
1) rdcu.be/Kw8d (@Chris_Barbieri1)
2) cell.com/cell/fulltext/…
3) cell.com/abstract/S0092… (@NCIgenomics)

A twitter explainer on our latest study, Inherited DNA Repair Defects in Colorectal Cancer – congrats @s_aldubayan @MattYurgelun @SapnaSyngal et al! @DanaFarber @broadinstitute @DamonRunyon @AJHGNews authors.elsevier.com/a/1Web9geWqOxr There’s an established heritability for colorectal cancer hovering around 30%, though only roughly 5-10% is explained by known syndromes involving genes like APC, MSH2, and PTEN, among others – the rest is so-called “missing heritability”

THREAD: @Twitter explainer on two new papers that, seemingly unrelated, show promise & perils of precision cancer medicine:
1) Immunogenomics & kidney cancer @sciencemagazine: science.sciencemag.org/content/early/…
2) Web-based genomics reporting @AMIAinformatics: academic.oup.com/jamia/advance-…
(1/n) First, the kidney cancer immunogenomics study: This tumor type has response rates to anti-PD-1 immunotherapy similar to other cancers, but not the same tumor genetics, e.g. mediocre mutational load, no focal amplification of PDL1