What We Fund

The Labrecque Foundation funds the most promising and innovative lung cancer research projects. Together with our research partners, we are working toward early detection methods that will diagnose lung cancer in Stage I or Stage II, when the five-year survival rate is 70% to 80%! Ongoing research projects funded by the Foundation include:

IN 2010, THE LABRECQUE FOUNDATION WAS AWARDED AN $1 MILLION GRANT FROM THE EARLY DETECTION RESEARCH NETWORK (EDRN), an initiative of the National Cancer Institute (NCI). The grant was presented to help fund a match program for which each organization contributed $1 million in research to investigate biomarkers for early detection of lung cancer in lifetime nonsmokers. Previous research shows that lung cancer is different in how it manifests in nonsmokers as opposed to smokers. In December of 2010, the Labrecque received notice that the EDRN intends to continue the program in 2011 with an additional $1 million match. The studies funded by this research will continue to progress the ability of identifying individuals as increased risk for lung cancer.

IN 2010 MEMBERS OF THE THOMAS G. LABRECQUE FOUNDATION / CANARY LUNG TEAM RECEIVED $4.2M IN FUNDING FROM THE DEPARTMENT OF DEFENSE CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS – LUNG CANCER RESEARCH PROGRAMS (CDMRP-LCRP) to expand the research currently being done on blood-based biomarkers for lung cancer early detection. The program is a two year study expanding the resources of TGLF/Canary in order to help advance results and accelerate timelines.

DR. DAVID HAYES, ASSISTANT PROFESSOR AT UNIVERSITY OF NORTH CAROLINA’S LINEBERGER CANCER CENTER is working to develop a diagnostic molecular test for non-small cell lung cancer (NSCLC), to reliably identify groups of tumors with different risks, patterns of tumor spread, and response to therapy. This ambitious undertaking on 2500 patients relies on assessing DNA and RNA in tumor cells while minimizing the contribution of normal surrounding cells. Thus far, half have been classified, and 350 tissue samples have been processed. There has been an unexpectedly robust result from the initial analysis. Subsets of samples have been sent to 24 expert pathologists in order to compare results determined by the molecular assay with traditional methods.

DR. DAVID KWIATKOWSKI, AT DANA-FARBER CANCER INSTITUTE is investigating the role of the TSC tumor suppressor genes in lung cancer. Disruption of the TSC genes leads to benign tumors and overgrowth of lung cells in 50% of cases. The signals from TSC pathway disruptions can be inhibited by the drug rapamycin, which would provide a new avenue of treatment for lung cancer. This study has now revealed that 22% of 80 tumor samples exhibit deficiency of TSC genes. Unexpectedly, a small proportion of the tumor samples had activation of the AKT pathway. Preliminary analysis indicates that this may be due to the loss of another tumor suppressor, PTEN, which inhibits AKT signaling. PTEN has not previously been implicated in lung cancer.

DISCOVERY

Under the direction of Dr. Gary Goodman and Dr. Mark Thornquist, the Carotene and Retinol Efficacy Trial (CARET) repository provides a specimen resource for discovery and validation of new serum biomarkers. CARET contains prospectively collected serum, plasma, and DNA from more than 1400 individuals who developed lung cancer. Dr. Samir Hanash is using proteomics to see what proteins are in the blood or other body fluids in lung cancer versus baseline. Initially his laboratory will discover proteins that are present uniquely in human blood samples prior to lung cancer diagnosis.

Dr. Harold Varmus and colleagues are using mouse models carrying mutations that have been shown to cause lung cancer in humans. Tumors in these mutant mice can be followed from initiation through progression and during tumor regression. Serum samples from these mutant mice at various stages will be analyzed using advanced proteomics techniques in order to identify potential biomarkers of early cancer development.

Dr. Jason Chien is identifying epidemiologic factors associated with an increased risk for developing lung cancer among women who never smoked. His study will comprehensively compare lung cancer risk factors among never, former, and current smokers to aid in designing screening strategies for never smokers and to indicate candidate lung cancer biomarkers for blood and imaging tests.

VALIDATION

Dr. Ite Laird-Offringa has found promising candidate genes that are modified by methylation in tumors of lung cancer patients but not in corresponding normal lung tissues. Her lab will further assess the performance of these candidate biomarkers in additional paired tissue and blood samples. Biomarkers that perform well in those tests will be tested on precious prospectively collected blood samples.

Development of assays to measure protein biomarkers is a major bottleneck in accelerating biomarkers through the pipeline to a blood test. Canary has addressed this bottleneck by funding a dedicated team to rapidly develop serum-based assays and validate candidate biomarkers. Promising biomarkers will be used in combination to provide the basis for tests using patient blood or body fluids.

IMPLEMENTATION

Dr. Sylvia Plevritis will use modeling to determine the required sensitivity and specificity of each component of combined blood-based and imaging-based tests in order to be both effective and cost-effective.

DISCOVERY

Dr. Sanjiv Gambhir and Dr. Jürgen Willmann are developing an advanced imaging technique that will light up lung cancer cells but not normal lung cells based on their unique molecular characteristics. This technique will not only have the resolution power to show extremely small lung lesions, but will also help to indicate whether the lung lesions identified show lethal, non-lethal, or benign characteristics.

VALIDATION

Future work will involve moving promising molecular imaging biomarkers into safety and efficacy studies in preparation for FDA-approved Investigational New Drug (IND) clinical trials.

IMPLEMENTATION

Dr. Peter Bach will examine cases of patients who died despite yearly CT screening to determine whether the window of opportunity is smaller than that interval to catch aggressive tumors.

In order to stimulate interest in screening for lung cancer at the public health level, we must show that screening would be effective and also cost-effective. Dr. Sylvia Plevritis will develop models to find out whether current imaging-based screening is effective and cost-effective using data from clinical trials. Together these studies will leave Canary investigators poised for further work, aimed toward additional biomarker discovery, further validation of combinations of biomarkers, and validation of imaging techniques. It will be critical to validate our biomarkers in patients or in samples from patients prior to cancer development, a true test of a marker for early detection. Ultimately these biomarkers-both imaging and blood tests-will be used for earliest detection of otherwise lethal lung cancer in smokers, non-smokers, and former smokers.