Current Grants

Each year, LCRF selects a group of grant recipients that demonstrate promise and ingenuity in their work. After receiving seed funding from LCRF, these researchers are often better prepared to demonstrate proof of concept and secure additional funding from governmental and other sources.

Learn more about current grant recipients below.

2017 Lung Cancer Research Foundation Annual Grant Recipients

Memorial Sloan Kettering Cancer Center

Principal Investigator:

Ashley Bakhoum, PhD

Research Project:

Targeting metastasis-initiating cells in lung adenocarcinoma

Summary:

Most cancer deaths are caused by metastasis - the recurrence of disease in organs distant from the primary tumor site.  Cancer cells may leave the primary tumor and spread throughout the body very early in disease progression, even before a patient’s initial diagnosis and treatment.  A subset of cells that survive the stress of spreading to a new environment may lie dormant for months to years before initiating a metastatic outgrowth. They are stem-like and often resist anti-cancer therapies, which primarily target dividing cells. The biology underlying these metastasis-initiating cells in lung cancer is poorly understood.  This proposal utilizes single-cell sequencing and multiplexed imaging approaches to identify where these metastasis-initiating cells reside and how they survive, evolve, and continuously evade detection by our innate immune defense system. A major problem facing the treatment of lung cancer is the emergence of metastasis or drug resistance arising from tumor cell heterogeneity.  By tackling single cell heterogeneity head-on, this proposal aims to transform how we define, think about, and treat lung cancer - ultimately, to develop therapies that may eradicate or control metastasis from its earliest stages of inception. 

Yale University

Principal Investigator:

Amy Davidoff, PhD

Research Project:

Patterns of palliative care and concurrent therapy for lung cancer at end-of-life: implications for quality

Summary:

This study will examine patterns of care during the final six months of life for Medicare beneficiaries who died from lung cancer. We will focus on the types of palliative care services received during this period, and the relationship to ongoing cancer-directed treatment, such as chemotherapy or radiation therapy. Palliative care is designed to manage symptoms of cancer and the side effects of treatment, and to reduce emotional distress for patients and families. While hospice has been a key provider of palliative care services, we will assess the extent to which palliative care is provided outside of the hospice setting. Several studies have suggested that early palliative care is associated with more patient-centered and less aggressive treatment at the end-of-life. Our study will examine this issue using a large, population-based dataset that includes almost 30% of Medicare beneficiaries. The results of this study will provide critical information on the current landscape of palliative care receipt and Medicare spending outside of hospice, and receipt of concurrent cancer-directed therapy. This research will allow refinement of quality measures related to end-of-life care. In addition, this research will help to guide development of new approaches to pay for palliative care within the Medicare program.

Massachusetts General Hospital

Principal Investigator:

Benjamin Drapkin, MD, PhD

Research Project:

Biomarker discovery for combination therapy with olaparib and temozolomide using patient-derived xenograft models of small cell lung cancer

Summary:

Small cell lung cancer (SCLC) afflicts more than 30,000 patients in the United States each year, and it is rapidly fatal in most cases. One of the challenges in developing new therapies is that even when outcomes are improved for a fraction of patients, there is no test to determine who will benefit. The goal of Dr. Drapkin’s project is to discover molecular features, or biomarkers, that can be used to predict benefit for experimental therapies. To discover these features, he has developed a platform to grow SCLC tumors from patients in mice using circulating tumor cells from blood. These models, called patient-derived xenografts (PDXs), are generated from patients entering clinical trials, both before treatment and after relapse. The PDX models can be studied to determine which features of the cancer predict response, and how the cancer becomes resistant. 

At Massachusetts General Hospital, an early phase clinical trial was recently launched to test the combination of the PARP inhibitor olaparib and the DNA damaging agent temozolomide (O/T), for patients with relapsed SCLC. This trial has shown promising early results, with just under half of the patients experiencing significant tumor shrinkage. PDX models derived from trial have been treated with O/T, and their responses mirror the trial patient responses. These models will be used to identify biomarkers of O/T sensitivity and mechanisms of O/T resistance. The immediate impact will be to improve the design of further clinical trials of O/T in SCLC patients. In the longer term, this project may represent a new paradigm for the rapid refinement of promising therapies in SCLC, in which a clinical trial can be studied in the laboratory in real time through a concurrent co-clinical trial in PDX models.

Weill Cornell Medical College

Principal Investigator:

Marcus Goncalves, MD, PhD

Research Project:

Molecular mechanisms of cachexia in non-small cell lung cancer

Summary:

Cachexia is a complex metabolic disorder defined by a dramatic loss in body weight and skeletal muscle tissue.  This condition is very common in non-small cell lung cancer where affected patients have reduced mobility, worsened quality of life, and shortened survival.  Therapeutic strategies to limit muscle loss are predicted to reverse these deleterious outcomes, independent of direct cancer treatment.  Cachexia has no effective treatment or known etiology, in part, because animal models poorly mimic the findings in patients.  Dr. Goncalves has identified and characterized a mouse model of non-small cell lung cancer that reliably replicates human cachexia.  During the course of the project, he will study the ways in which lung tumors directly alter the endocrine system and lead to changes in ketone metabolism and stress hormone (glucocorticoid) levels.  The results of this project will further the understanding of how cachexia develops and will highlight new dietary and therapeutic strategies on which to base future treatment.

Massachusetts General Hospital

Principal Investigator:

Haichuan Hu, MD

Research Project:

Targeting the tumor microenvironment to enhance non-small cell lung cancer targeted therapy

Summary:

Lung cancer tumors are not composed of tumor cells alone, but rather an integrated collection of both tumor and non-tumor cells (namely stromal cells).  It has been increasingly recognized that there is constant “crosstalk” between these two major cell populations. A variety of signal molecules are released by each component and orchestrate different biological effects on each other. Such crosstalk consequently awakens alternative survival machinery in tumor cells and substantially compromises the efficacy of mainstream cancer therapies. 

Deciphering and accordingly blocking intra-tumor crosstalk provides an enchanting yet rarely explored opportunity to enhance cancer therapies. Dr. Hu’s research aims to decode intra-tumor crosstalk by leveraging a novel approach that allows tumor and stromal cells from individual patients to grow side-by-side in a lab dish. That makes it possible for researchers to listen in on each cancer’s different conversations and tease out the relevant signals, informing the design of personalized pharmaceutical interventions. 

Yale University

Principal Investigator:

Nikhil Joshi, PhD

Research Project:

Investigating anti-tumor T cell function in autochthonous models of lung adenocarcinoma

Summary:

Most lung cancer patients are diagnosed with advanced stage cancer. But, most of what goes on in lung cancer patients occurs before cancer is found. Dr. Joshi uses animal models to investigate early tumors, and to study how immune cells change as lung tumors develop into advanced stage cancers. His goal is to understand why immunotherapy causes immune cells to kill lung cancer in some patients but not others. To date, studies in lung cancer patients show they respond better to immunotherapies when the tumors have a protein called "PD-1 ligand." The reason for this is not understood, but Dr. Joshi and his team think that "PD-1 ligand" may help the lung tumors to become cancers in the first place by turning off immune cells that should kill tumor cells. However, tumor cells can kill immune cells, and by turning them off, "PD-1 ligand" might actually keep them from dying. Immunotherapy turns the immune cells back on, so "PD-1 ligand" might keep immune cells around so they are able to respond to immunotherapy. This process is strongly tied to whether patients respond to immunotherapy, and therefore Dr. Joshi's work will help uncover the mysteries of why immune cells in cancer are broken, with a goal of fixing the broken immune cells to help patients survive lung cancer.

*This project was awarded the LCRF Scientific Merit Award, acknowledging the investigator whose proposal was selected for outstanding overall merit by LCRF's Scientific Advisory Board. 

Washington University

Principal Investigator:

Christopher Maher, PhD

Research Project:

Understanding the regulatory roles of long non-coding RNAs in lung cancer

Summary:

To date lung cancer research has primarily focused on the deregulation of protein-coding genes as potential diagnostic and therapeutic targets thereby missing the emerging role of long non-coding RNAs, which do not generate proteins. Using recent technological advances, the Maher lab has discovered multiple long non-coding RNAs that are altered in the tumors of lung cancer patients relative to normal tissue. Since our understanding of how lncRNAs function in cancer is still in its infancy, the Maher lab is pursuing the hypothesis that lncRNAs can function by binding with proteins and guiding them throughout the genome to regulate genes promoting cancer. To test this, the Maher lab will dissect how lncRNAs interact with protein complexes and subsequently manipulate long non-coding RNAs to alter the ability of a protein to promote oncogenic phenotypes. Overall, a better understanding of how long non-coding RNAs enable primary tumors to invade and metastasize could lead to the development of more specific treatments, such as targeting a lncRNA directly, to improve patient outcomes.

**This project was awarded the LCRF William C. Rippe Award for Distinguished Research in Lung Cancer, acknowledging the investigator whose proposal not only demonstrates exceptional scientific merit but also exemplifies an enduring commitment to making an impact in the field of lung cancer research.

The University of Texas MD Anderson Cancer Center

Principal Investigator:

Triparna Sen, PhD

Research Project:

Investigating the role of DNA damage repair inhibition in enhancing anti-tumor immunity in small cell lung cancer

Summary:

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that accounts for 14% of lung cancer cases. Despite decades of active research, treatment options for SCLC are limited. Recent efforts to expand the therapeutic arsenal toward SCLC have focused in part on immunotherapy, particularly immune checkpoints inhibitors, which are drugs that unleashes an immune system attack on cancer cells. However, overall response rates to immune checkpoint blockade remain poor. DNA damage repair (DDR) proteins helps a cell identify and correct damage to the DNA molecule. Drugs that target these DDR proteins like PARP and CHK1 have provided exciting new therapeutic options for the treatment of SCLC. Recent clinical data illustrating that defective DDR, predicts improved response to immune checkpoint blockade (anti-PD-1) supports the hypothesis that the addition of a DDR inhibitor to an immune checkpoint inhibitor may significantly enhance response rates and outcomes. This proposal seeks to study the key interactions between DDR targeting and anti-tumor immune response in SCLC. Dr. Sen will leverage a large, integrated set of laboratory and patient samples that will significantly accelerate and magnify the potential impact of the work. At completion, this study will- (1) Improve mechanistic understanding of how targeting DDR enhances anti-tumor immune response; (2) Identify of novel immunotherapy combinations; and (3) Detect biomarkers to identify SCLC patients who will most likely respond to DDR+ immunotherapy combinations. The goal is to translate this approach for improved treatment options of SCLC patients.

Dana-Farber Cancer Institute

Principal Investigator:

Alison Taylor, PhD

Research Project:

Genome engineering to generate models of chromosome arm-level aneuploidies in lung cancer

Summary:

Most healthy cells have 46 chromosomes, which carry DNA within the cell. However, almost 90% of tumors have cells with an incorrect number of chromosomes, termed “aneuploid” cells. Some whole chromosomes or large chromosome fragments may be duplicated or lost. It has been shown that aneuploidy is a contributing factor in the formation of cancers. Interestingly, different chromosomes are often affected in distinct tumor types. For example, one half of chromosome number 3 is lost in some types of lung cancer, but this is not a common feature of breast cancer. Using a new laboratory technology that cuts chromosomes at specific locations, a large piece of chromosome 3 can be deleted in lung cells. Cells with and without this deletion can then be tested for differences in cell growth and other characteristics. Information from patient lung tumor samples can also be analyzed to identify distinct features correlating with specific chromosome changes. These studies will better define the effects of chromosome alterations and uncover new ways that cells can become cancerous. A better understanding of additional paths to disease formation will be critical for designing new cancer treatments.

New York University School of Medicine

Principal Investigator:

Hua Zhang, MD, PhD

Research Project:

Enhancing anti-PD-1 immunotherapy with CDK7 inhibition in small cell lung cancer

Summary:

Small cell lung cancer (SCLC) is one of the deadliest human cancers, accounting for about 15% of all lung cancers. Although SCLC patients often initially respond to chemotherapy, unfortunately tumors nearly always recur, resulting in a 5-year survival rate of less than 10%. Using syngeneic immunocompetent mouse models with high resemblance to patient disease, Dr. Zhang will identify new therapeutic targets whose inhibition could augment anti-tumor immunity by PD-1 immunotherapy. In addition, to gain a deeper molecular insight of the immune landscape, Dr. Zhang will measures the transcriptional profiles of all tumor and immune cells by single-cell RNA-sequencing induced by treatment. Ultimately, characterizing the underlying mechanism associated with drug sensitivity will help develop tailored treatments for SCLC patients.