Non-small cell lung cancer (NSCLC)

The most common type of lung cancer

Lung cancer detection by CRISPR-based detection of circulating tumor DNA

This grant was funded in part by Schmidt Legacy Foundation and Upstage Lung Cancer
Edwin Yau, MD, PhD
Roswell Park Cancer Institute
Buffalo

Currently,  computed tomography (CT) is available as a tool for the early detection of lung cancer in high-risk individuals. Unfortunately, it has a high false-positive rate: less than 5% of people with nodules found through CT actually have lung cancer. Apart from the distress associated with false positives, individuals may have to undergo invasive procedures, such as a biopsy, to rule out lung cancer.

Circulating tumor DNA (ctDNA) is DNA released from dying cancer cells into the bloodstream. Individuals with early-stage lung cancer may have ctDNA in their blood, even when the cancer is localized. CRISPR-Cas technology is a novel DNA modifying tool that can be used to develop sensitive, specific, and economic ctDNA assays. Dr. Edwin Yau will develop a CRISPR-Cas-based blood test to detect ctDNA in the blood of individuals suspected of having lung cancer. While the immediate goal of the project is to evaluate this blood test in individuals who have already undergone a CT scan, the ultimate goal of the project is to develop a blood test for screening all individuals.

Development of markers to predict response to immunotherapy in NSCLC

Jeffrey Thompson, MD
University of Pennsylvania
Philadelphia

Currently, three immune checkpoint inhibitors are approved by the FDA for the treatment of a subset of advanced-stage NSCLC. However, immunotherapy is a costly treatment regimen and comes with a unique side effect profile because of the inhibitors’ ability to cause inflammatory tissue damage. At present, the PD-L1 protein is used as a biomarker to predict which patients may respond to immunotherapy. Unfortunately, presence or absence of PD-L1 protein may not be an accurate predictor of response. Dr. Jeffrey Thompson is studying how we can develop more accurate biomarker signatures that may not only predict response to immunotherapy but may also determine which patients will develop treatment-related side effects. He will develop a novel blood-based liquid biopsy approach that will enable doctors to predict which patients will respond to immunotherapy drugs.

Immunometabolic T cell profiling as a prognostic liquid biopsy in NSCLC

Kellie Smith, PhD
Johns Hopkins School of Medicine
Baltimore

Checkpoint inhibitors, a type of immunotherapy, are now available in the first-line and second-line settings for certain subsets of NSCLC patients. Furthermore, the U.S. Food and Drug Administration recently approved an immunotherapy-combination treatment regimen for the treatment of a subset of advanced-stage NSCLC patients. While we are making progress in combining and sequencing immunotherapy with other conventional treatments, it is still unclear which patients will respond to these combinations. Dr. Kellie Smith’s laboratory is studying immune cells in blood samples from patients who have received the recently approved combination therapy. She postulates that immune cells from patients receiving the combination behave very differently from immune cells from patients who have received single-agent immunotherapy. Dr. Smith’s team will identify and exploit these differences to develop a blood test that will help predict which patients may benefit from combination therapies, thereby sparing patients the exposure to ineffective treatments.

Targeting the Complement Pathway in ALK Positive Lung Cancer

This grant was funded by ALK Positive
Raphael Nemenoff, PhD
University of Colorado Denver
Aurora

Overcoming Innate Immune Resistance in ALK-Rearranged Lung Cancer

This grant was funded by ALK Positive
Justin Gainor, MD
Massachusetts General Hospital
Boston

Characterization of Anti-ALK Immunologic Responses in ALK-Positive NSCLC

This grant was funded by ALK Positive
Mark Awad, MD, PhD
Dana-Farber Cancer Institute
Boston

Intercept Lung Cancer Through Immune, Imaging & Molecular Evaluation-InTIME

Grant title (if any)
SU2C-LUNGevity Foundation-American Lung Association Lung Cancer Interception Dream Team
This grant was co-funded by Stand Up to Cancer, LUNGevity, and the American Lung Association
Avrum Spira, MD, MSc
Boston University
Boston
Steven Dubinett, MD
UCLA
Los Angeles
CA
Julie Brahmer, MD
Johns Hopkins Kimmel Cancer Center
Baltimore
MD
Sam Gambhir, MD, PhD
Stanford University
Palo Alto
CA
Matthew Meyerson, MD, PhD
Harvard/Dana-Farber Cancer Institute
Boston
MA
Charles Swanton, PhD
Francis Crick Institute
London, England

The SU2C-LUNGevity Foundation-American Lung Association Lung Cancer Interception Dream Team, led by LUNGevity SAB member Dr. Avrum Spira, is developing a combination of diagnostic tools, such as non-invasive nasal swabs, blood tests, and radiological imaging, to confirm whether lung abnormalities found on chest imaging are benign lung disease or lung cancer.

Integrated Blood-Based and Radiographic Interception of Lung Cancer

Grant title (if any)
SU2C-LUNGevity Foundation-American Lung Association Lung Cancer Interception Translational Research Team
This grant was co-funded by Stand Up to Cancer, LUNGevity, and the American Lung Association
Lecia Sequist, MD
Massachusetts General Hospital
Boston
Max Diehn, MD
Stanford University
Palo Alto
CA
Tilak Sundaresan, MD
Kaiser Permanente San Francisco
San Francisco
CA
Gad Getz, PhD
Broad Institute
Cambridge
MA

The SU2C-LUNGevity Foundation-American Lung Association Lung Cancer Interception Translational Research Team, headed by LUNGevity Scientific Advisory Board (SAB) member Dr. Lecia Sequist, is developing a lung cancer interception assay (LCIA) that can be used in conjunction with low-dose CT scans. This assay will be based on an integration of several blood-based assays that examine circulating tumor cells and circulating tumor DNA.

Overcoming heterogeneity and resistance in EGFR-mutant NSCLC

Zofia Piotrowska, MD
Massachusetts General Hospital
Boston

Targeted therapies have become a mainstay of treatment for non-small cell lung cancer patients whose tumors test positive for a targetable driver mutation. The EGFR mutation is one such targetable mutation. New third-generation EGFR inhibitors have recently entered the clinic and can be very effective therapies for some patients who develop resistance to first- and second-generation EGFR inhibitors. Unfortunately, we are now seeing that cancer cells can also learn how to outsmart these third-generation inhibitors, and new and more effective treatments are needed. Dr. Zofia Piotrowska is studying how lung cancer cells become resistant to third-generation EGFR inhibitors, such as osimertinib, and how the heterogeneity of EGFR-mutant lung cancers can contribute to resistance to drugs like osimertinib. During the period of this award, Dr. Piotrowska will also be conducting a clinical trial testing a novel drug combination developed to prevent or delay the development of drug resistance among patients with EGFR-mutant lung cancer.

Dynamics of neoantigen landscape during immunotherapy in lung cancer

This grant was funded in part by the Schmidt Legacy Foundation
Valsamo Anagnostou, MD, PhD
Johns Hopkins University
Baltimore

The lung cancer treatment landscape is rapidly evolving with the advent of immunotherapy. Checkpoint inhibitors, a class of immune-targeted agents, are now available in both the first-line and second-line settings for certain subsets of lung cancer patients. However, the fraction of patients achieving a durable response remains low and, even among patients who respond, the majority develop resistance. Dr. Valsamo Anagnostou is using a comprehensive approach employing genome-wide and functional immune analyses to identify mechanisms of resistance to immune checkpoint blockade. In addition, she is developing a blood-based molecular assay utilizing serial blood samples of lung cancer patients to more accurately predict response and resistance to these therapies.