Mutation profile

Laboratory tests that identify changes at the level of DNA and help decide course of treatment 

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.

Overcoming ALK resistance with covalent cysteine-reactive inhibitors

A. John Iafrate, MD. PhD
Massachusetts General Hospital
Boston
Liron Bar-Peled, PhD
Massachusetts General Hospital and Harvard Medical School
Boston
MA

Overcoming bypass signaling to enhance clinical responses in ALK-positive lung cancer

Ibiayi Dagogo-Jack, MD
Massachusetts General Hospital
Boston

Predictive biomarkers of radio-immunotherapeutic response in NSCLC

Sean Pitroda, MD
The University of Chicago
Chicago

Dr. Pitroda and his team will develop a biomarker signature that can predict which patients are the most likely to benefit from an immunotherapy-radiation therapy combination. The ultimate goal is to determine which patients are likely to benefit from this combination treatment.

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.

Genome Alterations Associated With Airway Premalignant Lesion Progression

Joshua Campbell, PhD
Boston University
Boston

One of the challenges for early detection and prevention of squamous cell lung cancer, a type of non-small cell lung cancer (NSCLC), is the lack of understanding of how premalignant lesions develop and progress to lung cancer. Dr. Campbell is studying how normal lung cells acquire changes in their DNA to form premalignant lesions. His ultimate goal is to develop a biomarker to predict development of squamous cell lung cancer.

Detecting early stage lung cancer with circulating tumor cells

Rajan Kulkarni, MD, PhD
Oregon Health and Science University (formerly at UCLA Medical Center)
Portland

Dr. Kulkarni is studying how circulating tumor cells (cancer cells that are released into the blood stream) can be used to develop a blood test for lung cancer early detection and treatment. Funding from LUNGevity will help him use a novel technology called the Vortex Chip to test two things: first, if lung cancer be detected early by identifying circulating tumor cells in the blood and second, if there are biomarkers in circulating tumor cells that can differentiate patients who will respond to immunotherapy or chemotherapy.

Mutational Analysis of the Tyrosine Kinome in Lung Cancer

Funded by LUNGevity Foundation in collaboration with The CHEST Foundation, the philanthropic arm of the American College of Chest Physicians
William Pao, MD, PhD
Memorial Sloan Kettering Cancer Center
New York

Dr. Pao’s research may determine whether specific mutations in tyrosine kinase genes make lung tumors vulnerable to EGFR-TKIs. A comprehensive analysis of the tyrosine kinase in lung cancers could also lead to new opportunities for drug development and more personalized molecularly targeted therapies.

Transposon Mutagenesis for Lung Cancer Gene Discovery

Funded equally by LUNGevity Foundation and the Illinois Chapter of the American Cancer Society
Timothy K. Starr, PhD
University of Minnesota Department of Genetics, Cell Biology and Development
Minneapolis

In order to identify mutated genes that cause lung cancer, Dr. Starr has developed a system that is capable of randomly mutating genes within cells, resulting in tumor formation. The genes mutated by this method can easily be identified using standard molecular biology techniques. He can then test their role in lung cancer formation.