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FINDING CURES TOGETHER<sup>SM</sup>

Targeting RAS-Driven Cancers

Sunday, Dec. 9

Monday, Dec. 10

Tuesday, Dec. 11

Wednesday, Dec. 12

Sunday, Dec. 9

Welcome and Keynote Address
7-8 p.m.

Welcome
Frank McCormick, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California

Keynote Address: Deconstructing K-RAS oncogenic signaling in lung and pancreatic tumors
Mariano Barbacid, Spanish National Cancer Research Center (CNIO),
Madrid, Spain

Opening Reception
8-9:30 p.m.


Monday, Dec. 10

Continental Breakfast
7-8 a.m.

Plenary Session 1: RAS Structure and Biophysics
Session Chair: Gideon Bollag, Plexxikon, Berkeley, California
8-10:40 a.m.

New structural insights into KRAS biology
Dhirendra K. Simanshu, Frederick National Laboratory for Cancer Research, Frederick, Maryland

KRAS Q61H preferentially signals through the MAPK pathway in non-small cell lung cancer
Kenneth D. Westover, UT Southwestern Medical Center, Dallas, Texas

Targeting RAS for anticancer therapy
Sharon L. Campbell, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Dimerization is critical for the functions of wild-type and mutant KRAS
Chiara Ambrogio, Dana Farber Cancer Institute, Boston, Massachusetts

Oncogenic Ras control of the tumor immune microenvironment
Julian Downward, Francis Crick Institute, London, United Kingdom

Novel state I structures of oncogeneic KRAS4b mutants bound to GTP analog*
Albert Chan, Frederick National Laboratory for Cancer Research, Frederick, Maryland

Speaker Panel Discussion

Break
10:40-11 a.m.

Plenary Session 2: KRAS Processing and Localization
Session Chair: Frank McCormick, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
11 a.m.-1:15 p.m.

KRAS4b's unique diffusion behavior is defined by plasma membrane and effector interactions
Thomas J. Turbyville, Frederick National Laboratory for Cancer Research, Frederick, Maryland

Lipid dependence of KRAS plasma membrane interactions
John F. Hancock, University of Texas, Health Science Center at Houston, Houston, Texas

Targeting K-RAS4B on biologic membranes
Mitsu Ikura, University of Toronto, Toronto, Ontario, Canada

Multiscale simulations of k-Ras on lipid bilayers
Fred H. Streitz, Lawrence Livermore National Laboratory, Livermore, California

Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer*
Sahar Nissim, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts

Speaker panel discussion

Poster Session A / Lunch
1:30-3:30 p.m.

Plenary Session 3: Lessons Learned from Mouse Models
Session Chair: Shiva Malek, Genentech, Inc., South San Francisco, California
3:30-5:45 p.m.

Tissue and cell-specific functions of Hras, Kras4A and Kras4B in skin and lung cancer
Allan Balmain, University of California, San Francisco, California

Targeting KRAS-dependent metabolic processes for pancreatic cancer treatment
Channing J. Der, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Targeting redox dependencies in pancreatic cancer
Christine Chio, Columbia University, New York, New York

Exploiting the metabolic dependencies of mutant KRAS lung tumors
Carla P. Martins, University of Cambridge, Cambridge, United Kingdom

Modeling the genetic heterogeneity of KRAS mutant lung
adenocarcinomas for therapeutic discovery*
Kate Sutherland, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia

Speaker panel discussion

Evening Off / Dinner on Own
5:40 p.m.


Tuesday, Dec. 11

Continental Breakfast
7-8 a.m.

Plenary Session 4: Targeting KRAS – Immunotherapy and Immunotargets
Session Chair: Karen M. Cichowski, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts
8-9:10 a.m.

T-cell receptors recognizing mutated RAS: Preclinical and clinical studies
James C. Yang, National Cancer Institute, Bethesda, Maryland

The interplay between RAS/MAPK signaling and tumor immunology
Priti S. Hegde, Genentech, Inc., South San Francisco, California

Speaker panel discussion

Plenary Session 5 I: Targeting KRAS and KRAS-Effector Complexes
Session Chair: Frank McCormick, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
9:10-10:50 a.m.

Targeting K-Ras directly
Kevan M. Shokat, University of California, San Francisco, California

Insight towards therapeutic susceptibility of KRAS mutant cancers from MRTX1257, a novel KRAS G12C mutant-selective small-molecule inhibitor
James G. Christensen, Mirati Therapeutics, San Diego, California

Unlocked groove—developing covalent inhibitors of KRASG12C
J. Russell Lipford, Amgen, Department of Oncology Research, Thousand Oaks, California

Break
10:50-11:10 a.m.

Plenary Session 5 II: Targeting KRAS and KRAS-Effector Complexes
Session Chair: Frank McCormick, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
11:10 a.m.-1 p.m.

Preventing KRAS processing
Frank McCormick

Leveraging RAF dimer inhibitors to target RAS mutant tumors
Shiva Malek, Genentech, Inc., South San Francisco, California

Selective contribution of the SHOC2 phosphatase complex to ERK pathway dynamics highlights its potential as a therapeutic target*
Isabel Boned Del Rio, University College London, Cancer Institute,
London, United Kingdom

Speaker panel discussion

Free Time / Lunch on Own
1-2:30 p.m.

Plenary Session 6: Identifying New Vulnerabilities and New Therapies
Session Chair: Karen M. Cichowski, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts
2:30-5:10 p.m.

Developing therapies for Ras-driven cancers
Karen M. Cichowski

Oncogenic Ras-dependent tumor cell vulnerabilities
Dafna Bar-Sagi, New York University Medical Center, New York, New York

Pancreatic cancer models and medicine
David A. Tuveson, Cold Spring Harbor Laboratory Cancer Center, Cold Spring Harbor, New York

Targeting KRAS mutant cancers
Jeffrey A. Engelman, Novartis, Cambridge, Massachusetts

Context dependent role of Kras in GI malignancies
Prasenjit Dey, MD Anderson Cancer Center, Houston, Texas

Combinations with CDK4/6 inhibitors to treat cancers with mutations in both KRAS and CDKN2A*
Sean Buchanan, Eli Lilly, Indianapolis, Indiana 

Speaker panel discussion

Poster Session B / Reception
5:25-7:25 p.m.

Evening Off / Dinner on Own
7:25 p.m.


Wednesday, Dec. 12

Continental Breakfast
7:30-8:30 a.m.

Plenary Session 7: Systems Approaches
Session Chair: Shiva Malek, Genentech, Inc., South San Francisco, California
8:30-10:45 a.m.

Systematic interrogation of KRAS in cancer
William C. Hahn, Dana-Farber Cancer Institute, Boston, Massachusetts

Global proteomics reveals the context-dependence of K-Ras signaling
Kevin M. Haigis, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Dissecting the playbook of cancer: Genomic analysis of 100,000 human tumors reveals elaborate patterns of activation of the RTK-RAS-MAPK pathway
Gerard Manning, Genentech, Inc., South San Francisco, California

Genetic Approaches for Testing Candidate Drug Targets for Ras-Induced Tumorigenesis in Vivo
Kevin M. Shannon, University of California, San Francisco, California

Combinatorial knockout of RA1GDS1 and RhoA leads to lethality in KRAS-driven non-small cell lung cancer*
Kaja Kostyrko, University of California, San Francisco, San Francisco, California

Speaker panel discussion

Break
10:45-11 a.m.

Plenary Session 8: Perspectives – Opportunities from Bench to Clinic
Session Chair: Gideon Bollag, Plexxikon, Berkeley, California
11 a.m.-12:35 p.m.

Interplay between RAF inhibitors and RAS
Ying Zhang, Plexxikon, Berkeley, California

Development of effective therapies for neurofibromatosis type 1 and other pediatric RAS-driven tumors
Brigitte C. Widemann, National Cancer Institute, Bethesda, Maryland

To Be Determined
Neal Rosen, Memorial Sloan-Kettering Cancer Center, New York, New York

Biochemical and structural analysis of the Neurofibromin (NF1) protein and a potential role for protein destabilization in Rasopathy diseases*
Dominic Esposito, Frederick National Laboratory for Cancer Research, Frederick, Maryland

Speaker panel discussion

Closing Remarks

*Short talk from proffered abstract

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