Dana Farber Cancer Institute
Principal Investigator: Matthew Meyerson, M.D., Ph.D.
Research project: "A New Treatment Target for Lung Adenocarcinoma"
Description: This proposal is to study a new tyrosine kinase target for lung cancer therapy called EPHA-3. EPHA-3 mutations have been discovered in 10% of adenocarcinomas of the lung, almost as common as EGFR mutations. (This study will validate this abnormality as a target for new treatments as well as potentially improving the results of current approved drugs.)

University of Chicago Medical Center *
Principal Investigator: Ralph R. Weichselbaum, M.D.
Research project: "MUC-1 Directed Cell Cycle Genes as Targets for DNA Damaging Agents in Lung Cancer"
Description: This proposal builds on prior LCRF funded research to identify new targets for treatment with either chemotherapy or radiation therapy for lung cancer. This work has concentrated on a family of gene changes commonly seen in lung cancer cell lines and patient specimens particularly resistant to current therapy. The goal is to discover mechanisms that reverse the resistance and afford more effective treatment.

University of Colorado Denver *
Principal Investigator: Rachel M.A. Linger, Ph.D.
Research project: "Novel Biologically Targeted Therapy for the Treatment of Lung cancer"
Description: This proposal extends the first phase of LCRF supported research by Dr. Linger into practical applications of treatment opportunities. It capitalizes on her outstanding productive work on a new target (Axl receptor tyrosine kinase) for the therapy of lung cancer and is on the cutting edge of potentially fundamental new advances in the disease.

Weill Cornell Medical College
Principal Investigator: Bhupesh Parashar, M.D.
Research project: "Early Prediction of Radiation Treatment Response in Lung Cancers Using a Novel Fluoro-choline PET"
Description: This study proposes to look at a new tracer molecule for PET scan. The new tracer molecule has the potential to distinguish between cell proliferation (e.g. cancer ) and inflammation (e.g. bacterial infection, radiation) which is difficult to accomplish with traditional FDG-PET. If positive as expected, the new test would be compared directly to the current method and could quickly become the new standard fro documenting response to lung cancer treatment around the world.

* This project has received second-year funding

In 2008, the LCRF conducted its first "open call" grant submittal process and as a result received numerous requests for funding from various institutions throughout the country, and from outside of the United States. Based upon NIH standard guidelines for scientific merit and originality of concept, with additional consideration given to the project's consistency with the mission of the LCRF, each submittal was reviewed by the LCRF Medical Advisory Board members. As a result of this review, the LCRF is pleased to award ten (10) grants, totaling $500,000, to the following institutions supporting the research work of the principal investigator(s) listed:

Columbia University Medical Center
Principal Investigator: Charles A. Powell, M.D.
Research project: "Molecular Features of Lung Adenocarcinoma Progression"
Description: Study of the effects of changes in chromosome 7q on the ability of lung cancer cells to become invasive. Early studies show that alterations in a specific chromosome in lung cancer cells are associated with a tendency to invade and spread into normal cell areas. This study proposes to better characterize specific effects in cells and potentially identify new opportunities for more effective therapies.

Dartmouth Medical School - Norris Cotton Cancer Center
Principal Investigator: Charles Brenner, Ph.D.
Research project: "Dissecting the Function of a Gene Expression Brake Pedal"
Description: Fhit as a regulator of Dnmt 1 expression. The Fhit gene is one of the earliest genes that seem to turn off in lung cancer. When the gene is turned off, the levels of a protein Dnmt1 rise in early lung cancer cells. This study proposes to investigate this phenomenon further to determine the role of Dnmt as a cause of lung cancer and potentially a future target for therapy.

Johns Hopkins University - Sidney Kimmel Cancer Center
Principal Investigator: Edward Gabrielson, M.D. and Julie Brahmer, M.D.
Research project: "A Novel Molecular Pathway as a Target for Lung Cancer"
Description: Mps1 is a critical enzyme necessary for the growth of lung cancer. This proposal will study whether blocking this enzyme can slow the growth of lung cancer in mice. If positive, it could lead to a potential new treatment for lung cancer.

M.D. Anderson Cancer Center
Principal Investigator: Joerg J. Jacoby, Ph.D.
Research project: "Study of HIF-1 Alpha as a Target for PX-478, a new drug for Lung Cancer"
Description: A new drug in early clinical trials for lung cancer will be studied in further detail to evaluate its action on lung cancer cells as well as identifying potential ways to determine which patients could be predicted as best candidates for the drug.
View Abstract

Memorial Sloan-Kettering Cancer Center *
Principal Investigator: Marc Ladanyi, M.D.
Research project: "Harnessing New Genomic Technologies to Understand Lung Cancer"
Description: The study of the impact of low expression of DUSP4 and EGFR mutations in lung cancer. Some lung cancers are now known to have EGFR mutations. A prior LCRF grant allowed identification of numerous other genes associated with various mutations in EGFR. This proposal will support a mouse model to identify the impact of what appears to be an important gMarene mutation combination in some lung cancers and how this effects the growth of such tumors in mice models. This understanding could lead to more effective treatments and new agents selective for these changes.

Tufts Medical Center
Principal Investigator: Christina Baik, M.D., MPH
Research project: "Effect of Reproductive Factors on the Development of Lung Cancer in Women"
Description: A prospective study of reproductive factors and the risk of lung cancer in women. Using a very large population base, the Nurses' Health Study, which includes detailed history of over 120,000 nurses, this study will evaluate the impact of reproductive issues in woman who develop lung cancer to those who do not. This includes factors such as the number of children born, age at first birth, age at menopause, etc.
View Press Release

University of Chicago Medical Center
Principal Investigator: Ralph R. Weichselbaum, M.D.
Research project: "Identification of Pathways Activated by Genes Encoding Resistance to Cancer Treatment"
Description: Non-small cell lung cancers (NSCLC) are highly resistant to radiotherapy and chemotherapy; however the basis for their lack of responsiveness to treatment is not known. Other studies have shown that MUC1 oncoprotein is over expressed in most NSCLC's and is associated with resistance to treatment and a poor prognosis. This study will employ bioinformatic tools to discover new pathways activated by MUC1, an important gene in blocking cell death by cytokines and chemotherapy. They hope to identify potential new therapeutic targets in lung cancer as well as other types of cancers in which MUC1 is expressed.
View Abstract

University of Michigan
Principal Investigator: Steven P. Zielske, Ph.D.
Research project: "Cell Therapy for Treatment of Radiation Therapy-induced Lung Injury"
Description: Effect of mesencymal cells as potential repair mechanism for damaged lung tissue. Mesencymal cells are naturally occurring stem cells that help repair damaged tissue in adults, e.g. in wound healing. This study proposes to access the potential use of high levels of mesenchymal cells to reduce the risk of radiation damage to lung tissue thus potentially allowing for higher doses of radiation.

Wayne State University
Principal Investigator: Maik Hüttemann, Ph.D.
Research project: "A Non-Invasive Gene Therapy for Lung Cancer"
Description: This proposal is for a new gene therapy for lung cancer using COX4-2 which appears to be an important and selective element for normal cells but missing in lung cancer cells. They propose that replacement of this gene in lung cancer cells could kill them. The proposal is to study this effect as well as a delivery model on how to get the gene to cancer cells.

* This project has received second-year funding


As a result of the 2008 Grant Awards, the LCRF proudly recognizes the cumulative impact of its funded support to worthy research endeavors throughout the country including projects emphasizing the biologic origins of lung cancer, future targets for therapy, gene therapy, genomics, development of potential new drugs for lung cancer as well as prevention and epidemiologic studies.