Adenocarcinoma

 The most common subtype of NSCLC

Molecular Characterization of Lineage Plasticity

Helena Yu, MD
Memorial Sloan Kettering Cancer Center
New York

As a mechanism of resistance to EGFR inhibitors, cancers can change histology from adenocarcinoma to small cell or squamous cell lung cancer. Once this happens, EGFR inhibitors are no longer effective treatment; there are no strategies currently available to prevent or reverse transformation after it has occurred. Dr. Yu will use advanced molecular techniques to identify genetic changes that contribute to transformation. Understanding these genetic changes will identify biomarkers that can be utilized to develop treatments to prevent and reverse transformation.

Targeting Drug Tolerant States + DNA Damage to Block Osimertinib Resistance

Christine Lovly, MD, PhD
Vanderbilt University Medical Center
Nashville

Despite high tumor response rates, patients treated with EGFR targeted therapies, such as osimertinib, inevitably develop disease progression. Mechanisms of drug resistance remain incompletely understood on both a genomic and proteomic level. The objective of Dr. Lovly’s project is to find new targeted treatments and drug combinations that can tackle cancer evolution and osimertinib resistance.

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.

Signaling Heterogeneity in Small Cell Lung Cancer

Jonathan Lehman, MD, PhD
Vanderbilt University Medical Center
Nashville

Chemotherapy has been the mainstay for treatment of small cell lung cancer (SCLC)—a highly aggressive subtype of lung cancer—for the past three decades. SCLC responds well to initial treatment but inevitably comes back. No targeted therapy is currently available for patients with SCLC. Dr. Lehman is studying how SCLC becomes resistant to chemotherapy. His research will further our understanding of chemotherapy resistance and identify novel targets for SCLC treatment.

Axl as a target to reverse EMT, treatment resistance and immunosuppression

Lauren Averett Byers, MD
MD Anderson Cancer Center
Houston
Don Gibbons, Jr., MD, PhD
MD Anderson Cancer Center
Houston
TX

Drs. Byers and Gibbons have discovered that lung cancer cells acquire the ability to hide from the immune system during epithelial-to-mesenchymal transition—a process through which cancer cells develop the ability to spread to other parts of the body (metastasis). The LUNGevity award will help Drs. Byers and Gibbons study the effect of a new drug that can reverse the EMT process and make lung cancer cells more visible to the immune system.

Lung screening via biophotonic analysis of nanoarchitecture of buccal cells

This grant was funded in part by Upstage Lung Cancer
Vadim Backman, PhD
Northwestern University
Evanston
Ankit Bharat, MBBS
Northwestern University
Evanston
IL

Cells in the respiratory tract are usually stacked in an orderly fashion. As lung cancer develops, the cells get “un-stacked” and their shapes change, giving them the ability to grow and spread to other parts of the body. Dr. Vadim Backman from Northwestern University is utilizing a new technology called Partial Wave Spectroscopy for seeing those cells. With the LUNGevity Early Detection Award, he will check how cells taken from the cheeks of stage I lung cancer patients reflect these early changes with the ultimate goal of using partial wave spectroscopy technology for early detection of lung cancer.

Dissecting novel mechanisms of lung cancer pathogenesis

Kathryn O’Donnell, PhD
UT Southwestern Medical Center
Dallas

Dr. O’Donnell has discovered that lung cancer cells make a protein called PCDH7 that is present on the surface of cancer cells where it may be accessible to therapies. In cooperation with the KRAS protein, the PCDH7 protein relays signals from outside the cell to make cancer cells grow faster. She is studying the function of the PCDH7 protein and developing strategies to reduce its effect on the KRAS pathway.

Exploring the therapeutic potential of novel KRAS inhibitors in lung cancer

Piro Lito, MD, PhD
Memorial Sloan Kettering Cancer Center
New York

Dr. Lito is working with a new drug that works efficiently to stop the growth of lung cancer cells with a mutation in the KRAS gene. Funding from LUNGevity will provide resources to test the drug in mice that have KRAS-positive lung cancer. Dr. Lito’s ultimate aim is to develop a clinical trial for the drug for use in patients who test positive for a KRAS mutation.