Targeted therapy

A type of cancer therapy that targets specific signals or molecules that make cancer cells grow abnormally fast

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.

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

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.

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.