Monday, October 17, 2022

9:00 am – 9:30 am:

Introduction & Welcome from

Deputy NCI Director – Doug Lowy

National Cancer Institute Director – Monica Bertagnolli

RAS Scientific Consultant – Frank McCormick


9:35 am – 12:40 pm:

What is the progress targeting RAS directly in the clinic (and what are emerging resistance mechanisms)? 

Overview of Targeting RAS in the clinic – Frank McCormick


“Targeting RAS in Cancer: Opportunities and Challenges”, presented by Andy Aguirre


“Determinants of sensitivity and resistance to KRAS inhibition”, presented by Piro Lito


What are RAS therapeutics in the pipeline?

“Novel Approaches to Target RAS”, presented by Eli Wallace


“Targeting the Active State of Oncogenic RAS Variants”, presented by Mark Goldsmith


“Beyond G12C: Opportunities to target additional KRAS mutant alleles in an expanded spectrum of human cancers”, presented by James Christensen


“Maximizing the benefit of KRASG12C inhibition:  Recent data & next steps”, presented by Brian Lanman


12:40 pm – 2:30 pm:

Lunch / Poster Session


*2:30 pm – 3:00 pm*

Meet the Expert Session

Andy Aguirre - conf rm E1204

Eric Tran - conf rm E1202

Mark Goldsmith - conf rm E1108

James Christensen - conf rm E1203

William Hahn - conf rm E1201

Brian Lanman - 3rd floor table

Piro Lito - 3rd floor table

Frank McCormick – 3rd floor table


3:00 pm – 5:25 pm:

Are there Alternative Strategies for Targeting RAS?


Targeting the SHOC2 Complex

“The SHOC2 phosphatase complex: a node for selective inhibition of the ERK pathway in RAS-driven cancers”, presented by Pablo Rodriguez-Viciana


“Systematic studies of RAS”, presented by William Hahn


“Structure of the SHOC2–MRAS–PP1C complex and therapeutic strategies”, presented by Dhirendra Simanshu


Immunology Strategy

“Targeting mutant KRAS with adoptive T-cell therapy”, presented by Eric Tran


Short Talks:

“Combining KRAS-G12C(ON) inhibitors with SHP2 and immune checkpoint blockade to overcome adaptive resistance and enhance anti-tumor immunity in lung cancer”, presented by Miriam Molina-Arcas


“RAS(ON) inhibitors overcome clinical adaptive resistance to KRAS G12C covalent blockade” presented by David Santamaria


“Direct Targeting of K-Ras-Membrane Interactions” presented by Johannes Morstein

Tuesday, October 18, 2022

9:00 am – 1:00 pm

What have we learned about RAS activation of RAF kinase?

“Structural characterization of a RAF-activating complex in Drosophila”, presented by Marc Therrien


“Structure and Function of RAF-family Kinases Probed via Live Cell Target Engagement”, presented by Arvin Dar


“ADMIRRAL – High performance computing meets RAS/RAF biology at the membrane”, presented by Dwight Nissley


“Targeting RAF1 in KRAS Driven Lung Tumors” presented by Mariano Barbacid


Short Talk:

“Role of RAS/CRAF interaction in RAS-driven lung cancer”, presented by Romain Baer               


What about RAS activation of other effectors? – Discussion panel

Julian Downward, Channing Der, Doug Lowy, Neal Rosen, Mark Philips

What is the evidence that RAS activates PI3K and/or other effectors (besides RAF)?   


Short Talks:

“Stabilization of the 14-3-3/CRAF Interaction for Inhibition of the MAPK Pathway”, presented by Holly Vickery


“RAS-PI3K signaling in CAFs impacts KRAS-driven lung cancer progression by controlling the physicochemical properties of the extracellular matrix”, presented by Esther Castellano


1:00pm – 3:00 pm

Lunch / Poster Session


*2:30 pm – 3:00 pm*

Meet the Expert Session

Julian Downward & Mark Philips - conf rm E1204

Mariano Barbacid - Conf rm E1202

Doug Lowy & Channing Der - Conf rm E1108

Arvin Dar - Conf rm E1203

Marc Therrien - Conf rm E1201

Lucy Young - 3rd floor table

Jana Ognjenovic - 3rd floor table

Pau Castel - 3rd floor table

Brigitte Widemann – 3rd floor table


3:00 pm – 5:25 pm

What have we learned about Regulation of RAS and NF1?

“Cryo-EM analysis of human NF1”, presented by Jana Ognjenovic


“Neurofibromin cryo-EM structure can be used to predict missense variants that disrupt protein stability”, presented by Lucy Young


“RAS and GPCR dysregulation contribute to benign tumorigenesis in Neurofibromatosis”, presented by Nancy Ratner


“Clinical trials targeting NF1 related manifestations: What have we learned?”, presented by Brigitte Widemann


Posttranslational Modifications and Isoforms

“TBD”, presented by Mark Philips


Short Talks:

“RAS Signaling Strength Determines Phenotypic Response”, presented by Amanda Moore


“Top-down Mass Spectrometry Reveals an Expanded RAS Proteoform Landscape in Malignant Cell Lines”, presented by Caroline DeHart


5:30 pm – 7:30 PM – Networking Event (open to all attendees)


Wednesday, October 19, 2022

9:00 am – 11:45 am

RAS in the membrane: what is the biological meaning of lipid mediated RAS nanoclusters?

“Lipid dependency of KRAS plasma membrane interactions”, presented by John Hancock


“How do RAS proteins cluster on the plasma membrane?”, presented by Alex Gorfe


"Biological relevance of wild-type/mutant KRAS complexes at the cell membrane”, presented by Chiara Ambrogio


“RAS-membrane interactions under biological nanoscopes”, presented by Xiaolin Nan


Short Talks:


“Membrane Curvature Manipulation for Oncogenic Ras Clustering in Cells, presented by Wenting Zhao


Complex lipid composition drives KRAS4b-Raf1 RBDCRD nanoclusters on the membrane”, presented by Rebika Shrestha


"In Vitro Reconstitution and Characterisation of Membrane-Associated KRAS4B-BRAF Complex Using Nanodiscs", presented by Ningdi Liu


Open Discussion – John Hancock moderating


11:45 am – 1:20 pm

Brunch / Networking


*12:50 pm – 1:20 pm*

Meet the Expert Session

Alex Gorfe – conf rm E1204

Sharon Campbell – conf rm E1202

John Hancock – conf rm E1203

Xiaolin Nan – conf rm E1201

Edward Stites – 3rd floor table

Chiara Ambrogio - 3rd floor table


1:20 pm – 2:40 pm

KRAS isoforms and mutant alleles – are there therapeutic opportunities?

“Mutants, Loners and Bad Influences” presented by Ed Stites


“Expanding the Scope of Direct Covalent K-Ras Inhibitors”, presented by Kevan Shokat


“Molecular Insights into Oncogenic NRAS-mediated Activation of RAF”, presented by Sharon Campbell


Short Talks:

“Biochemical and Functional Analysis of Mutations Within the α4-α5 Allosteric Lobe of RAS to Examine Their Role in RAS Dimerization” presented by Michael Whaby


“KRAS mutant allele cycling rates and selectivity of inhibitors”, presented by Matthias Samwer


2:40 pm – 3:15 pm

Frank McCormick, Symposium Wrap Up & Highlights