Onc fellow @MSKCancerCenter w/ #PDAC #GIOnc interest | #medchem 💊 PhD | 🐶 dad | @OslerResidency @umnmstp @dartmouth alum | 🏳️🌈 he/him | #mdphd
New York, NY
Joined July 2019
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Finally published! Thanks to all the co-authors for their monumental efforts and the reviewers who helped make this story better. Of all the science I've done to date, I'm the most proud of this. #medchem #allosteric 1/2
nature.com/articles/s41586-0…
Aside from helping ALK-driven NSCLC turn into a chronic disease, I'm intrigued by many brushed over aspects of this story:
1. Screening for glues via CRBN-directed 4k library - would love to know more and what other targets have been tested...
1/2
2. No direct measureable affinity between lead compound and ALK - many companies would have killed the project then but thankfully they kept pushing!
3. Also initial hit didn't degrade the target in cells - could have also killed the project!
#medchem
2/2
Another win for olanzapine and for many patients
ascopubs.org/doi/abs/10.1200…
Practice changing as editorialized? If true equipoise is believed, maybe time for prospective evaluation
ascopubs.org/doi/10.1200/JCO…
Exciting stuff for patients - now can't wait to see what the combo with chemo shows a la Flaura2
nejm.org/doi/full/10.1056/NE…
Nice example of ligand-based drug design to discover #PPI inhibitors of "smooth" proteins, e.g. #RAS-RAF, & incorporation of protein NMR to show allosteric binding effects. Next would like to see a Cys selectivity screen and improved affinity. #medchem
nature.com/articles/s41467-0…
Erik Faber MD PhD retweeted
The best part of #AACRPanc26: the people. 💜 
Mentors and mentees.
Friends and collaborators.
Scientists, clinicians and patient advocates.
Different perspectives, one ☝️united front🛡️against #PancreaticCancer.
Science brings us together.
Friendship and shared purpose keep us moving forward.
Grateful for this community. @AACR
#PDAC #KRAS #TeamScience
💜 @MSK_DeptOfMed @MSKCancerCenter @CpcrMsk @PanCAN @lustgartenfdn @NatPancFdn @Pankind_Aus
@EileenMOReilly @Jonathanwlee23 @BenWestphalen @GIcancerDoc Collin Weekes @OncoDailyGI @oncodaily
We need more of this type of work looking at differences between primary lesion and intrahepatic metastases in understudied #cholangiocarcinoma for development of better #TME targeting treatments
ovid.com/10.1097/HEP.0000000…
Phenomenal work using basic chemical principles/ techniques to target Q61X #RAS. Love the 90s science inspiration and work determining MoA of their activator including key base positioning.
Maybe next gen includes small bicyclic heterocycles? Could further lock in base position
Bronsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants
nature.com/articles/s41589-0…
Erik Faber MD PhD retweeted
The National Science Foundation (NSF) has issued a 10-page memo signaling a retreat from its traditional role of giving grants to individual researchers to pursue their best ideas and to train the next generation of scientists.
Instead, the memo makes clear, NSF will devote the bulk of its resources to addressing the research priorities of President Donald Trump and his administration, many of them technology focused. scim.ag/4ipE1kY
Good #medchem example of targeting pseudokinases to #allosteric-ally regulate #PPI / #kinase activity. Reassuring is decent kinome selectivity despite targeting the ATP-binding site, and would love to see further development of C160 covalent activators.
cell.com/cell-chemical-biolo…
We now need more of this forward looking work in #PDAC
While the unique importance of anti-CTLA4 over other ICB is intriguing, I doubt we'll see trials with single agent anti-CTLA4 - at least dual ICI may be reasonable to try with select #RAS inhibitors
nature.com/articles/s41467-0…
Erik Faber MD PhD retweeted
Among patients with previously untreated metastatic #ColorectalCancer, adding high-dose vitamin D3 to standard chemotherapy plus bevacizumab did not improve progression-free survival compared with standard-dose vitamin D3.
Objective response and overall survival were also similar between groups.
ja.ma/4yfVsZT
Erik Faber MD PhD retweeted
The association of COVID vax, ICI, and improved survival was too good to be true:
“the previously reported vaccination survival advantage is largely explained by selection bias, with patients who had more favorable prognoses more likely to receive the SARS-CoV-2 vaccination…”
Now online: Deconvolving SARS-CoV-2 mRNA Vaccine Impact on Immunotherapy-Related Survival doi.org/10.1158/2159-8290.CD…
Of course this work is intriguing for a very very select patient. But the disparities in Table 1 re: medical Hx make me skeptical that #SDOH weren't at least partially responsible for difference in outcomes.
jamanetwork.com/journals/jam…
Erik Faber MD PhD retweeted
Now FDA finally delivered!!
Please welcome 🎂 the new birth of 💫 “RASONque”
Congrats 🎉🎊 to every investigator, nursing teams, research teams and courageous patients! #pancreaticcancer #PDAC
@MSKCancerCenter @MSK_DeptOfMed @CpcrMsk @EileenMOReilly @MichaelMayMD @MarcHilmi @FiyinfoluB @schoenfeld_j @AnupriyaSingha9
fda.gov/news-events/press-an…
Seemingly practice-changing and reassuring for the use of YEARS in pts w/ cancer - a whopping 22% (!) were able to forgo CTPA safely
jamanetwork.com/journals/jam…
Of the 3 organoid papers in @Nature, this was my favorite w/ the comparison to PDX and 2D + detailing of PDAC MUC program and Wnt. While yes, model + culture conditions affect adhesion etc, we should now focus less on model accuracy and more on utility
nature.com/articles/s41586-0…
Will be very interesting to see how this correlates to clinical samples - also reiterates how difficult it is to re-sensitize resistant tumors to therapy #CDK8 #KRAS
link.springer.com/article/10…
