Erik Faber MD PhD

Onc fellow @MSKCancerCenter | #medchem 💊 PhD | 🐶 dad | ex-HS teacher 🧑‍🏫 | @OslerResidency @umnmstp @dartmouth alum | 🏳️‍🌈 he/him | #mdphd #GIOnc

[Erik Faber MD PhD @fabermdphd]

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

[Gunda I. Georg @gunda_i]

Congratulations to all co-authors. DOI 10.1038/s41467-023-38732-x

[NEJM @NEJM]

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

[Erik Faber MD PhD @fabermdphd]

TBH I had no idea we were underfunding #sclc and #nsclc research by so much, but also this may all soon be out of date as it appears the NIH may not fund much of anything anymore😭

https://t.co/MmoYrjI3IS

[Erik Faber MD PhD @fabermdphd]

A must-read for anyone interested in drug development #medchem

We'll need to track/measure if drugs from NAM improve the historically poor success rate of translation from bench to bedside, and if so, in what ways (efficacy, safety, etc)

https://t.co/yt9JzAjMcc

[Erik Faber MD PhD @fabermdphd]

Well, this is intriguing and easy enough to do...and could save those on-call fellows some extra work

https://t.co/fqr2BrMld5

[Erik Faber MD PhD @fabermdphd]

Just getting around to this intriguing data
https://t.co/keihwy9bS9

Dreams for the future:
- synchronous biopsies of 1⃣ tumor and metastases
- differences b/w liver v lung v other sites
- progression biopsies while still on therapy to better study resistance

[NEJM @NEJM]

In a phase 1–2 study of daraxonrasib, treatment-related adverse events of grade 3 or higher occurred in 30% of patients with previously treated RAS-mutated pancreatic cancer, and up to 35% of patients had an objective response. Full study results: https://t.co/q296mEbKy1

Science behind the Study: Advances in RAS Therapeutics for Pancreatic Cancer https://t.co/rDDjGqRJtL

[Erik Faber MD PhD @fabermdphd]

Intriguing observation re: loneliness as an outcome predictor in oncology - and further notes the need for patients from rural communities.

But also underestimated may be the social power of urbanization, which we should consider encouraging.

https://t.co/QUX4qIpmSy

[Erik Faber MD PhD @fabermdphd]

Want to improve #mdphd #doubledocs training, especially for IM-bound folks?

Probably just eliminate MS4 year - would be interesting to study performance in this group that often has their med school years interrupted

https://t.co/LEJ3FuUTEe

[Wafik S. El-Deiry, MD, PhD, FACP @weldeiry]

Dr. Charles Sawyers speaks at #AACR26 Plenary Session about overcoming resistance through an approach that addresses lineage plasticity in prostate and other tumors.

He recounted Enzalutamide, discussed elegant genetic mouse models of neuroendocrine prostate cancer involving PTEN, p53, and Rb.

He then described a next-gen organoid based transplantation model of neuroendocrine prostate cancer (Romero et al Nature Cancer 2024).

He described insights into organoids growth conditions, ECM, integrins and neuroendocrine transitions.

YAP1/TAZ, TEAD, and hippo signaling gave insights to therapeutic intervention to reverse neuroendocrine differentiation. LATS, TEAD, and Notch inhibitors have been emerging from the organoid approach.

Sustained YAP/TEAD, Notch and AR inhibition with Enzalutamide drove NEPC differentiation in vitro. Altered TEAD and FOXA1 binding occurs towards NEPC specific enhancers.

DLL3 and LATS inhibitor were proposed for lineage restoration therapy.

[Erik Faber MD PhD @fabermdphd]

https://t.co/EX5sC903W3

Things I like about this:
- Use of phenotypic screening
- Upfront counterscreening for selectivity
- Notable CAF-mediated MOA:⬆️ #ECM organization, collagen metabolism
- Immediate translation into trials

Also how long did this all take to do?... #medchem

[Anirban Maitra @Aiims1742]

🚨🚨🚨
RASOLUTE-302 Ph3 is POSITIVE
"Daraxonrasib demonstrated a median OS of 13.2 months versus 6.7 months for chemotherapy, with a hazard ratio of 0.40 (p < 0.0001)".... WOW!

AMAZING news for patients with #PancreaticCancer
The RAS Revolution is ON!!
https://t.co/I59NNWRB1O

[Erik Faber MD PhD @fabermdphd]

Lots to be gleaned from this:

https://t.co/G9fUbrYk0W

But importantly appears that allostery in #kinases can be underestimated by cell-free kinase panels, especially for non-type I inhibitors #medchem

[Cancer Research @CR_AACR]

New in the April 1 issue from the Cancer Research special series: Transcriptomic Plasticity Is a Hallmark of Metastatic Pancreatic Cancer https://t.co/nQugWzMJnz
@arnavmehta3 @centralparkwmd @EileenMOReilly @ciacobu @dana_peer #OpenAccess

[Erik Faber MD PhD @fabermdphd]

#GPCR remain a major target of small molecules, and this review rightly demonstrates the promise of drugging adhesion GPCRs. This could be especially impt in cancer, where we now appreciate the #TME, #ECM, integrin signaling, mechanotransduction, etc.

https://t.co/eBbXogOv44

[Erik Faber MD PhD @fabermdphd]

https://t.co/vEVC5jUABM

As a former #peptide chemist turned small mol chemist, I know this took tons of work. Lessons learned re: peptides:

- ⬆️Lipophilic = better always, generally
- PPB may be key
- PK = major issue

Also SPR exp w/ cyclins...would love to know the method

[Wungki Park, MD MS @CentralParkWMD]

1/n Now published in @NatureMedicine : The phase 2 #POLAR trial of pembrolizumab + olaparib maintenance in metastatic pancreatic cancer. @CpcrMsk @MSKCancerCenter @MSK_DeptOfMed @PICIatMSK
https://t.co/Fo0Rn6FGzZ

[Erik Faber MD PhD @fabermdphd]

Work like this further convinces me the #ECM is more than a scaffold - it is a signal

https://t.co/q3UEuSXEbP

[The Osler Medical Residency @OslerResidency]

Thrilled to welcome the next generation of Oslerian physicians— a group dedicated to the pursuit of excellence, to becoming master clinicians & growing through rigor, and to being leaders in medicine! welcome to the Osler Medical Residency & the Osler family! #oslerpride

[The Osler Medical Residency @OslerResidency]

Also thrilled to share the future leaders of the Osler Resideny—our 2027-2028 ACSs! @maxmcgredy @jackbuyske @mahamkaratela @Liam_P_Coyne @helminthhenry . Our ACSs are the heart of the program & embody our mission and values. We are in great hands with these 5 amazing people!

[Erik Faber MD PhD @fabermdphd]

I can't tell you how many surgeries I've been in where we've debated for quite some time if a structure was vessel or nerve...

Really cool #medchem work that I think has translational potential

https://t.co/saCijfiEM2