Targeting KRAS Mutant Lung Cancers Dream Team - Stand Up To Cancer

Dream Teams

Research  >  Research Portfolio  >  Dream Teams  >  Targeting KRAS Mutant Lung Cancers Dream Team

SU2C–American Cancer Society Lung Cancer Dream Team: Targeting KRAS Mutant Lung Cancers

Grant Term: August 2015–January 2021

The SU2C-ACS Lung Cancer Dream Team has established a collaborative, scientifically rigorous, multidisciplinary program that brings together the two highly promising treatment approaches of targeted therapy and immunotherapy. This combined KRAS targeted, immunotherapy approach should lead to novel therapies that will markedly improve outcomes for patients.

Supported by:

ABOUT THIS TEAM’S RESEARCH

Mutations in the KRAS gene are found in 20 to 25 percent of lung cancers. These cancers do not respond well to standard lung cancer treatments and are notoriously difficult to treat. Researchers have been developing new drugs that specifically target biological pathways disrupted by mutant KRAS. In addition, some drugs belonging to a class of drugs called immune checkpoint inhibitors, have been approved for a number of cancers including lung cancer. The goal of the Dream Team has been to develop and bring together these two highly promising therapeutic approaches of targeted therapy and immunotherapy.

The Team is currently conducting numerous clinical trials, including trials of novel KRAS G12C inhibitors and studies evaluating combinations of targeted therapies (e.g., KRAS G12C, MEK inhibitors) with checkpoint inhibitors that are specific for the PD-1 receptor.

To maximize the benefit of immunotherapy, the Team is also analyzing samples from patients that have been treated with this class of drugs. The Team seeks to identify ways to predict which patients are more likely respond to immunotherapy.

SEE SCIENTIFIC ABSTRACT

MEET THE TEAM

The top scientists and researchers on the SU2C–ACS Lung Cancer Dream Team come from a variety of backgrounds and disciplines, which leads them to great insights upon collaboration. Learn more about the SU2C–ACS Lung Cancer Dream Team.

Jedd Wolchok, MD, PhD
Co-leader
Memorial Sloan Kettering Cancer Center
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Pasi A. Jänne, MD, PhD
Co-leader
Dana-Farber Cancer Institute
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Justin F. Gainor, MD
Co-leader
Massachusetts General Hospital Cancer Center
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Dream Team Members

Jedd D. Wolchok, MD, PhD
Memorial Sloan Kettering Cancer Center
Co-leader

Pasi A. Jänne, MD, PhD
Dana-Farber Cancer Institute
Co-leader

Justin F. Gainor, MD, PhD
Massachusetts General Hospital Cancer Center
Co-leader

Drew Pardoll, MD, PhD
Johns Hopkins University
Principal Investigator

David Gandara, MD
University of California, Davis
Principal Investigator

Gad A. Getz, PhD
Broad Institute
Principal Investigator

Roy Herbst, MD, PhD
Yale University
Principal Investigator

John Heymach, MD, PhD
MD Anderson Cancer Center
Principal Investigator

Frank McCormick, PhD
University of California, San Francisco
Principal Investigator

Drew M. Pardoll, MD, PhD
Johns Hopkins University
Principal Investigator

Charles Rudin, MD, PhD
Memorial Sloan Kettering Cancer Center
Principal Investigator

Lalitha Ramanathapuram
Memorial Sloan Kettering Cancer Center
Project Manager

Cam Anh Tran
Dana-Farber Cancer Institute
Project Manager

Andrea Ferris
LUNGevity Foundation
Advocate

Jeffrey Wigbels
The Cypress Group at Morgan Stanley
Advocate

“
”

“Lung cancer is the number one cancer killer in the United States among both men and women, new treatment approaches are urgently needed.”

Otis W. Brawley, MD, former chief medical and scientific officer
American Cancer Society

TEAM PROGRESS UPDATES

Stand Up To Cancer’s research projects are designed to foster collaborative, swift translational research. The hallmarks of these efforts include rigorous application and selection procedures, sufficient funding to allow scientists to focus on the objectives of the grant, and reviews by senior scientists every six months. These reviews help the investigators capitalize on the latest findings, address potential roadblocks, and collaboratively evolve as the science requires. Please click on the link to see summaries of research results so far for the SU2C–ACS Lung Cancer Dream Team.

TEAM PROGRESS UPDATES

PUBLICATIONS

Clinical acquired resistance to KRASG12C inhibition through a novel KRAS switch-II pocket mutation and polyclonal alterations converging on RAS-MAPK reactivation.
Noritaka Tanaka, Jessica J. Lin, Chendi Li, et al (2021).
Cancer Discov. 2021 Apr 6;candisc.0365.2021. doi: 10.1158/2159-8290.CD-21-0365.
A burned-out CD8+ T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy.
Miguel F Sanmamed, Xinxin Nie, et al (2021)
Cancer Discov. 2021 Mar 3;candisc.0962.2020. doi: 10.1158/2159-8290.CD-20-0962.
A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers.
Gettinger, S. N., Choi, J., Mani, N et al (2018).
Nature communications, 9(1), 3196. doi:10.1038/s41467-018-05032-8
Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.
Hyejin Choi, Jiehui Deng, Shuai Li, Et al (2019)
Cell Rep. 2019 Apr 16;27(3):806-819.e5. doi: 10.1016/j.celrep.2019.03.066.
Clinical activity of programmed cell death 1 (PD-1) blockade in never, light, and heavy smokers with non-small-cell lung cancer and PD-L1 expression ≥50.
J.F. Gainor, H. Rizvi, E. Jimenez Aguilaret al (2020)
Ann Oncol. 2020 Mar;31(3):404-411. doi: 10.1016/j.annonc.2019.11.015.

CLINICAL TRIALS REFERRALS

Cancer clinical trials allow researchers to study innovative and potentially life-saving new treatments. The goal is to find treatments that are better than what’s currently available; in fact, the therapies offered to today’s cancer patients were almost all studied and made possible by people participating in clinical trials. But many cancer clinical trials aren’t completed because not enough people take part.

At StandUpToCancer.org/ClinicalTrials, you’ll find clinical trial information, answers to common questions, and a free clinical trial finder tool.

 

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