Beth Israel Deaconess/Harvard Medical School
Principal Investigator: Ming Chen, PhD/Pier Paolo Pandolfi, MD, PhD T
Research project: The role of DOK 2 L138S in lung cancer susceptibility
Description: Study of a lung cancer suppressor gene that when altered may lead to higher rates of lung cancer particularly in smokers.


2011 LCRF SCIENTIFIC MERIT AWARD
Dana Farber Cancer Institute/Harvard Medical School
Principal Investigator: Adam Bass, MD T
Research project: Finding new therapeutic targets in squamous lung cancer
Description: The investigator has discovered a new oncogene, SOX2, associated with squamous cell lung cancer. The grant will support the work to identify the essential co-factor needed to allow the gene to function which is not yet known. Knowledge of this target could potentially lead to more effective therapy for the cancer.

Dana Farber Cancer Institute/Harvard Medical School
Principal Investigator: Donald Kufe, MD T*
Research project: Development of a new therapy for lung cancer that has become resistant to current drugs
Description: This grant extends previous LCRF support to study the MUC-1 oncoprotein, which is often found in high levels in lung cancer that are associated with shorter survival and resistance to common current treatments. Inhibitors to MUC-1 will be now evaluated in animal models and early human clinical trials to see if they are effective in decreasing the growth of these aggressive cancers.

Massachusetts General Hospital/Harvard Medical School
Principal Investigator: Anthony Faber, PhD B
Research project: Understanding the PI3Kinase pathway in lung cancer
Description: The PI3Kinase pathway is a critical central regulator f cancer cell growth and survival. He will investigate several inhibitors of the pathway in lung cancers that have specific gene mutations as a method to predict which therapies would be most effective in such patients.

MD Anderson Cancer Center/University of Texas
Principal Investigator: James Welsh, MD C*
Research project: Using a circulating biomarker as a sign of treatment resistance in lung cancer
Description: Certain biomarkers such as miR-200 are thought to be predictive of the development of resistance to treatments for lung cancer such as radiation and chemotherapy. This grant extends previous LCRF support to evaluate whether this biomarker can provide useful clinical information on patients undergoing treatments such as radiation and biologic therapy.

MD Anderson Cancer Center/University of Texas
Principal Investigator: Humam Kadara, PhD T
Research project: Study of the ETS-2 oncoprotein in lung cancer patients who have never smoked
Description: The grant will study this protein in patients with lung cancer who have never smoked where preliminary results imply it is more common than in smokers. If confirmed, the grant will explore the impact of the protein on various pathways within the cell attempting to associate the findings with effective therapy. The findings could lead to specific recommendations for patients with this protein.

Memorial Sloan Kettering Cancer Center
Principal Investigator: Jamie Chaft, MD C
Research project: Can specific biomarkers (SNP's) in a lung cancer specimen identify patients likely to respond to chemotherapy?
Description: The grant will collect data from lung cancer patients attempting to identify markers that are associated with resistance and response to commonly used chemotherapy drugs in lung cancer. Ideally a predictive score could be used to assist clinicians in deciding which patients may have best chemotherapy responses and lead to considering alternative options otherwise. The model is based on recent success in applying the score to patients with urologic cancers.

Memorial Sloan Kettering Cancer Center
Principal Investigator: Jamie Ostroff, PhD C
Research project: Supporting the effective disclosure of lung cancer diagnosis by smokers to family and friends
Description: Smokers often are stigmatized when diagnosed with lung cancer as carrying personal responsibility for the disease as a result of their smoking. This leads to increased stress and coping difficulties at the time of diagnosis and throughout treatment. This grant will study the prevalence of this setting, create an interventional tool to assist in the disclosure of the diagnosis in smokers and then test the intervention in clinical settings.

Ottawa Hospital Research Institute
Principal Investigator: Christina Addison, PhD T
Research project: Testing the efficacy of various drug combinations in lung cancer with EGFR expression
Description: 90% of patients with lung cancer have high levels of EGFR yet the majority do not have significant response to EGFR inhibitors. This grant will study some of the co-factors responsible for blocking the expected effects. Knowledge of the presence and action of these co-factors could be used to identify patients who are not candidates for such therapy and lead to alternative options.

Rush University Medical Center
Principal Investigator: David Sher, MD, MPH C
Research project: Quality of Life and Costs of Care for patients receiving stereotatic radiation for lung cancer
Description: Some patients with early stage lung cancer receive stereotactic radiation therapy (high doses of RT given over 3-5 treatments) as an alternative to surgery. The grant will study this group of patients in regard to quality of life and costs of care compared to the alternative. As more patients become diagnosed with early stage lung cancer, it is becoming critical to comparative differences of treatment options.

The Ohio State University
Principal Investigator: Erica H. Bell, PhD T
Research project: Understanding the relationship between a common mutation in lung cancer and treatment response
Description: This grant will study the mutation involving BRG1 which has been described in 20-30% lung cancers. The abnormality will be evaluated in terms of its impact on cancer cell growth and also how it affects the response to drugs for the treatment of lung cancer. Further knowledge of this mutation may lead to specific treatment recommendations for patients with this mutation.

University of Medicine and Dentistry of New Jersey
Principal Investigator: Carol S. Lutz, PhD B
Research project: Is there a difference in a common metabolic pathway in lung cancer compared to normal cells?
Description: The regulation of the COX-2 pathway is a complicated vital pathway for all cells. The grant will study potential differences in lung cancer cells compared to the normal mechanism. Deeper understanding of these differences could lead to interventional opportunities for treatment.

University of Chicago
Principal Investigator: Ralph Weichselbaum, MD T*
Research project: Targeting the JAK/Stat axis to improve radio and chemosensitivity of lung cancer
Description: This grant expands support of prior LCRF funding to study the potential of inhibitors to a common mutation found in lung cancer as a means of improving the response to radiation and chemotherapy. By decreasing potential resistance to such treatments in patients with this abnormality, it is hoped improved treatment outcomes will occur.

University of Kentucky
Principal Investigator: Esther P. Black, PhD B*
Research project: How do certain mutations affect the development of lung cancer metastases?
Description: This a renewal of a LCRF grant to continue studying the effect of specific mutation changes in adenocarcinomas of the lung (miRNA's) as it relates to the tendency for the cancer cells to metastasize to distant locations. Understanding of this mechanism is critical in designing more effective therapy options.

University of Louisville
Principal Investigator: Jorge Gomez-Guitterez, PhD B*
Research project: Using viral therapy as a platform for lung cancer therapy
Description: The grant extends LCRF funding for gene based therapy models using viral transfer for lung cancer. It is hoped this highly specific directed therapy could achieve effective elimination of lung cancer cells with potentially less side effects compared to traditional methods. This grant will study the additive benefit of an additional viral vector to earlier work.

University of Minnesota:
Principal Investigator: Daniel Saltzman, MD, PhD B
Research project: Immunotherapy for lung cancer delivered by bacteria
Description: Study of a model to use bacterial carriers as a means of delivering immunotherapy stimulants to kill lung cancer cells. Salmonella bacteria which have been eliminated of any toxic effects by bioengineering will be used to carry the potentially effective cytokines to the lung cancer cell targets.

University of Pennsylvania
Principal Investigator: Xianxin Hua, MD, PhD T
Research project: Treatment of aggressive lung cancer with a novel combination of drugs
Description: Lung cancer patients with a mutation called K- RAS have aggressive tumors that are resistant to commonly used treatments. The grant will study the effects of interfering with several preliminary mechanisms that lead to the K-RAS mutation as a means of blocking this mutation and causing more effective elimination of the lung cancer.

University of California Irvine
Principal Investigator: Sergei Grando, MD, PhD B
Research project: Treatment of lung cancer using inhibitors of nicotine receptors
Description: The grant supports the study of blocking nicotine receptors that are known to be involved in transforming normal cells into lung cancer in some cases. The impact of this inhibition will be studied as a potential opportunity for therapy for lung cancer.

University of Texas Southwestern Medical Center
Principal Investigator: Puneeth Iyengar MD, PhD B
Research project: Identification of method to predict which lung cancers will be associated with weight loss and appetite loss
Description: Cachexia is a condition associated with many lung cancers characterized by significant weight loss, appetite decrease and overall weakness. This condition is often associated with lower rates of treatment response compared to other patients. The grant will use animal models to study potential predictive markers for the condition which could lead to clinical preventative measures in such patients during the cancer treatment period.

Vanderbilt University Medical Center:
Principal Investigator: Jun Qian, PhD B
Research project: Study of a common mutation in squamous cell lung cancers
Description: The grant will explore more details regarding their on-going interest in a mutation of the 3Q chromosome found in many lung cancers. It has been described as a mutation that causes increased growth and survival advantages to the cancer cells. Better understanding of the impact of this mutation could lead to potential inhibitors of this effect.

B = Basic Science
T = Translational
C = Clinical

* Renewal grant

American College of Chest Physicians
Description: To support the 3rd ACCP Lung Cancer Guidelines Conference in 2011.

2010 LCRF SCIENTIFIC MERIT AWARD
Dana-Farber Cancer Institute **
Principal Investigator: Donald W. Kufe, M.D.
Research project: "Development of a New Therapy for Lung Cancer Resistant to Existing Therapies"
Description: To explore the mechanism by which a new compound likely to be tested in humans can destroy lung cancer cells resistant to current drugs. By understanding these pathways, it may be possible to select lung cancer patients who will be most sensitive to its effect.

Dana-Farber Cancer Institute *
Principal Investigator: Matthew Meyerson, M.D., Ph.D.
Research project: "Understanding Genetic Mutations in Lung Cancer"
Description: To study genes that are frequently mutated in lung cancer as possible targets for creating improved therapy for lung cancer. This grant will support work that has been previously supported by the LCRF.

Duke University Medical Center
Principal Investigator: Michael J. Campa, Ph.D.
Research project: "Identifying an Immune Response in Patients with Lung Cancer"
Description: This lab will explore their recent discovery of an immune marker that appears to predict patients with lung cancer who do not demonstrate a tendency for their cancer to spread outside of the lung. By better understanding how this mechanism may work, it may be possible to use this knowledge for more effective outcomes of care.

Memorial Sloan-Kettering Cancer Center
Principal Investigator: Yixuan Gong, Ph.D.
Research project: "A Study of How Common Mutations in Lung Cancer Genes may Cause this Cancer"
Description: They will study the associated effects of the two most common gene mutations in lung cancer. A deeper understanding of how these gene abnormalities affect cell activities may lead to insights of more successful therapy.

Pennsylvania State University
Principal Investigator: Arun Sharma, Ph.D.
Research project: "Creating a New Drug for Lung Cancer"
Description: A new class of drugs with early evidence of positive effect in lung cancer cell growth will be tested in animal models to better understand how it is working and what subtypes of lung cancer might be most affected.

Stanford University
Principal Investigator: Viswam S. Nair, M.D.
Research project: "Studying the Genetic Nature of Lung Cancer in Patients Who Have Very Positive PET Sans at the Time of Diagnosis"
Description: PET scans are commonly used in patients who have a diagnosis of lung cancer to stage the extent of their disease. Patients with high PET scan uptake often have more aggressive disease than patients with lower levels of uptake. This study will evaluate genetic differences between such patient groups as a means of potentially identifying factors that lead to different natural history of the disease.

University of Chicago Medical Center
Principal Investigator: Ralph R. Weichselbaum, M.D.
Research project: "Understanding Genetic Markers in Lung Cancers as Potential Ways to Improve Response to Therapy"
Description: To study how micro RNA’s regulate sets of genes that are associated with aggressive forms of lung cancer. This understanding could lead to therapeutic opportunities to interfere with these relationships and cause cell destruction.

University of Florida
Principal Investigator: Bradford S. Hoppe, M.D.
Research project: "How Does a New Form of Radiation therapy (proton therapy) Cause an Immune Response to Lung Cancer?"
Description: It is now recognized that radiation therapy can cause an auto-immune effect against lung cancer cells. That could possibly enhance cell destruction beyond the radiation effect itself. They propose to study this mechanism as related to proton therapy which is an emerging new type of radiation treatment. Their findings could lead to predictions regarding patients who may respond more effectively to radiation therapy.

University of Kentucky
Principal Investigator: Esther P. Black, Ph.D.
Research project: "A Study of the Genetic Characterization of Lung Cancer that Could Affect the Tendency to Metastasize"
Description: They will explore the interactions of cells called tumor associated macrophages. These cells are thought to affect the ability of a lung cancer cell to grow beyond its local environment. Better understanding of the immune function of these cells and their effect on the genetic makeup of lung cancer cells may lead to new therapy options.

University of Louisville
Principal Investigator: Jorge G. Gomez-Gutierrez, Ph.D.
Research project: "A New Model for Viral Therapy for Lung Cancer"
Description: Their research focuses on a new method for potentially more effective viral gene transfer to treat lung cancer. Their work represents a model for highly specific targeted therapy aimed at interrupting specific cell pathways unique to lung cancer cells thus possibly avoiding damage to non-cancer cells.

University of Pittsburgh *
Principal Investigator: Christopher Bakkenist, Ph.D.
Research project: "Targeting Lung Cancer by Inhibiting Pathways of DNA Repair"
Description: This grant continues prior support of LCRF in identification of ways to block a cellular pathway that appears commonly associated with lung cancer cell growth. Better understanding of the blocking effect and associated cell death could lead to new therapy for lung cancers that display this pathway.
In February of 2011, Dr. Bakkenist was awarded a Research Project Grant (RO1) from the National Cancer Institute in the amount of $1.8 million.

University of Texas, MD Anderson Cancer Center
Principal Investigator: John V. Heymach, M.D., Ph.D.
Research project: "Understanding What Genetic Mutations in Lung Cancer are Functionally Important"
Description: There has been a large increase in genetic mutations identified in lung cancer cells compared to normal cells. Many of these gene changes are inter-related and dependent upon each other. This grant request proposes to apply a technique that could characterize the most significant gene alterations that affect cell function and growth. If successful, this could potentially lead to better stratification and prioritization of gene targets for research in lung cancer.

University of Texas, MD Anderson Cancer Center
Principal Investigator: Humam Kadara, Ph.D.
Research project: "Understanding the Genetic Signature of Lung Cancer in Non-Smokers"
Description: Non-smoker lung cancer is the 7th leading cause of death worldwide. There is strong evidence that the genetic makeup of such cancers differs from that of smokers and this grant will support more detailed evaluation of these differences.

University of Texas, MD Anderson Cancer Center
Principal Investigator: James W. Welsh, M.D.
Research project: "Developing a New Method of Reducing Resistance to Lung Cancer Therapy"
Description: Recent discoveries have identified a potential way that lung cancer cells not only become resistant to treatment with radiation or drugs, but also develop an ability to develop metastases. This proposal will study that mechanism in detailed models with the aim of applying this new information to techniques to reduce resistance of the cancer to effective therapy but also to potentially block the development of distant sites of disease.

* This project has received second-year funding
** This project was awarded the LCRF Scientific Merit Award acknowledging the investigator whose proposal was selected for outstanding overall merit by the LCRF Medical Advisory peer review.