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.

2019 LCRF Pilot Grant Recipients

Fred Hutchinson Cancer Research Center

Principal Investigator:

Alice Berger, PhD

Research Project:

Novel strategies for therapeutic target discovery in lung cancer

Summary:

Recent advances in understanding the human genome have led to successful new "precision oncology" for the treatment of lung cancer, such as the use of EGFR-targeted therapies in EGFR-mutant lung cancer. The discovery and application of these therapies has motivated a continued search for novel drug targets in these and other lung cancers. The foundation of these searches are high-throughput methods for genetic screening. However, traditional target discovery experiments can only query a single gene’s involvement in cancer. Some genes with redundant functions would not be identified in these traditional studies. The goal of this project is to identify genetically redundant genes in the human genome and to identify gene pairs that are required for resistance to EGFR-targeted therapies.

This work will directly help the tens of thousands of patients with EGFR-mutant non-small cell lung cancer. Increasingly, genomic information leads to “repurposing” of drugs developed for other diseases. If drugs already exist for some of the targets that are identified in our study, they can be repurposed for lung cancer therapy, and our work could positively impact lung cancer patients in less than five years. If therapies do not already exist, our work will provide the preliminary evidence that these genes/proteins would be worth investment from pharmaceutical companies, thereby serving a vital role of academic research and promoting the development of new lung cancer therapies.

University of Florida

Principal Investigator:

Lingtao Jin, PhD

Research Project:

The role of protein kinase signaling in cisplatin-resistant ASCL1-high subtype SCLC

Summary:

Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Due to very limited improvements in SCLC therapy or survival over the past 30 years, SCLC has been categorized as a recalcitrant cancer. Platinum-based chemotherapies, which are the standard of care for SCLC patients, usually lead to a robust initial clinical response, but the majority of patients quickly become resistant to therapy. Therefore, identification of critical factors responsible for the emergence of resistance to chemotherapy will not only provide personalized treatment options, but also help to identify cancer patients who may or may not benefit platinum-based chemotherapies. Dr. Jin’s lab recently found that a protein called MAST1 promotes the development of resistance to platinum treatment in SCLC. They found that MAST1 abundance correlates with platinum resistance in SCLC cell lines and patient tumors. Initial studies suggest that MAST1 may regulate cancer cell cycle progression and increase cancer cell survival ability in response to platinum treatment. Therefore, it is important to further decipher the role of MAST1 signaling in driving platinum resistance. In addition, Dr. Jin’s group will validate MAST1 as a therapeutic target to overcome platinum resistance. They found that a drug called CEP-701, which inhibits MAST1 activity, is effective in killing small cell lung cancer cells when combined with platinum. They will further evaluate the efficacy of CEP-701/platinum combination therapy in small cell lung cancer cell lines and animal models, and develop next generation of MAST1 inhibitors that may be used to treat platinum-resistant small cell lung cancer.

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

Princess Margaret Cancer Centre / University of Toronto

Principal Investigator:

Benjamin Lok, MD

Research Project:

Investigating a resistance mechanism mediated by a Skp, Cullin, F-box containing E3 ubiquitin ligase complex in small cell lung cancer

Summary:

Small cell lung cancer (SCLC) is a particularly aggressive subtype that represents approximately 15% of all lung cancers. Despite an initial response of SCLC to therapy, disease recurrence often occurs, and cure is rare, with dismal 5-year overall survival rates of about 7%. There is a critical need to understand the mechanisms of therapeutic resistance to develop more effective treatments for this disease. We have found that loss of a key component of a protein recycling complex leads to resistance to chemotherapy and a newer therapy, known as a PARP inhibitor, in SCLC. Here, we propose to understand more about how this protein recycling complex regulates DNA repair through experiments to precisely determine its impact on DNA damage and repair. Through these efforts, we seek to further our understanding of how cancer cells repair, tolerate and become resistant to our current treatments while designing newer treatment approaches to improve outcomes for our patients.

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

Memorial Sloan Kettering Cancer Center

Principal Investigator:

Zhan Yao, PhD

Research Project:

Studies on the oncogenic function and mediation of drug resistance by ARAF in lung cancer

Summary:

Despite the significant clinical benefit of epidermal growth factor receptor (EGFR, a receptor tyrosine kinase) inhibitors, primary and acquired resistance are commonly seen in lung cancer patients with EGFR activating mutations. Among those patients, ~20% tumors progress upon treatments by unknown mechanisms. By analyzing the genome sequencing data of the lung cancer patients with acquired resistance to EGFR inhibitors, Dr. Yao and his colleagues at MSKCC identified ARAF amplification as a new genetic event that may be responsible for the drug resistance. They observed that ARAF could activate RAS, a major effector of EGFR, through disrupting the binding of NF1 (a negative regulator of RAS) to it. Thus, the elevation of ARAF protein in cells could promote the RTK-mediated RAS activation and the downstream pathways that are required for cell proliferation or differentiation. Current data suggest, in EGFR mutant lung tumors, ARAF amplification likely causes the drug resistance by activating RAS signaling. Dr. Yao seeks to explore the detail functional consequences of ARAF activation of RAS in lung cancers and determine its role in the regulation of drug sensitivity. In addition, patient-derived xenograft models will be used to investigate therapeutic strategies for treating the ARAF-dependent drug resistance.

2019 LCRF Research Grant on Disparities in Lung Cancer

Vanderbilt University Medical Center

Principal Investigator:

Melinda Aldrich, PhD, MPH

Research Project:

Identifying determinants of racial disparities in lung cancer stage

Summary:

Racial disparities in lung cancer stage of diagnosis are well-documented. Fewer African Americans than whites are diagnosed at early-stage lung cancer, when better treatment options are available. Studies in patients seeking care at community health centers are limited and as a result, the causes of disparities in stage among the most vulnerable patients are poorly understood. This project will provide a deeper understanding of which factors influence lung cancer stage of diagnosis among community health center patients and provide outreach to the community about the importance of early detection for lung cancer.

Stanford University

Principal Investigator:

Manali Patel, MD, MPH

Research Project:

Reducing Disparities in Lung Cancer through Community Partnerships

Summary:

Scientific advances continue to reduce rates of new lung cancer cases and death from the disease. However, populations with low income as well as racial and ethnic minorities continue to experience high rates of lung cancer cases and lung cancer death. One potential cause for ongoing disparate outcomes from lung cancer includes inequitable receipt of evidence-based lung cancer care. Studies over the past decade repeatedly show lower receipt of stage-appropriate lung cancer care among low-income and minority populations as compared with non-Hispanic white and the more affluent. Previously, we demonstrated the role of social support in improving lung cancer survival for Hispanic populations and developed a novel approach, the CARE (Community health workers Activate, Reach, and Engage) intervention, to utilize social support to engage patients in their care and improve access to end-of-life cancer care for low-income and minority patients with advanced stages of cancer. The objective of this project is to refine, implement, and evaluate CARE with patients and caregivers in community oncology practices to increase access to evidence-based lung cancer recommendations from diagnosis until the end-of-life. The hypothesis is that this approach is feasible and acceptable in the community and can improve patients’ quality of life and reduce lung cancer outcome disparities.

University of Colorado Denver AMC

Principal Investigator:

Betsy C. Risendal, PhD

Research Project:

Improving Preventive Care to Address Lung Cancer Disparities

Summary:

National data suggest that only 4% of people who could benefit have received lung cancer screening, and that differences in the uptake of screening may further widen existing disparities in lung cancer survival. In pilot work funded by the Specialized Program in Research Excellence (SPORE) in Lung Cancer at the University of Colorado Cancer Center, significant barriers to implementing lung cancer screening programs were identified at the patient, provider and system-level. In the current project funded by the Lung Cancer Research Foundation, these barriers will be addressed by providing education, technical assistance and outreach to increase the uptake and delivery of this life-saving preventive screening.

Icahn School of Medicine at Mount Sinai

Principal Investigator:

Rajwanth Veluswamy, MD, MSCR

Research Project:

Assessing the mechanisms underlying the association between sex and immunotherapy response

Summary:

Recently, immune checkpoint inhibitors have become a mainstay in the treatment of advanced non-small cell lung cancer (NSCLC) after demonstrating unprecedented clinical activity in several large clinical trials. However, data from a systematic analysis of these trials suggest that females may have less response to immune checkpoint inhibitors than experienced by males. If validated, this finding will highlight the need to explore new immunotherapy regimens specific for women. Furthermore, understanding differences in immunotherapy efficacy amongst females vs. males may also reveal important underlying mechanisms of therapeutic immunity and potentially even provide targets for future synergistic immunotherapy combinations. This proposal intends to use advanced statistical modeling and cutting-edge laboratory techniques to 1) determine if female sex is independently associated with decreased immunotherapy efficacy in patients with advanced lung cancer, 2) determine if differences in the pre-treatment composition of the tumor immune microenvironment (TIME) is responsible for the association of sex and immunotherapy, and 3) study the role of hormones such as estrogen as a mediator in the relationship between sex and immunotherapy response. Elucidating these potential important mediators of immunotherapy response will have significant implications in guiding the treatment and future study of immunotherapy in lung cancer.

2019 Lung Cancer Treatment Focused Research Grant Program

University of Virginia

Principal Investigator:

Ryan Gentzler, MD

Research Project:

Real-time monitoring and modeling of symptoms and adverse events in lung cancer patients receiving oral targeted therapies for tumors with oncogenic driver mutations

Northwestern University Feinberg School of Medicine

Principal Investigator:

Nisha Mohindra, MD

Research Project:

Using the novel 4R patient care sequences to improve the duration and outcomes of therapy in NSCLC patients receiving targeted treatment

University of Pennsylvania

Principal Investigator:

Katharine Rendle, PhD, MSW, MPH

Research Project:

Implementation strategies for monitoring adherence in real-time (iSMART)

University of Maryland, Baltimore

Principal Investigator:

Christian Rolfo, MD, PhD, MBA

Research Project:

Proactive monitoring of treatment-related adverse events through a mobile application in NSCLC patients treated with tyrosine kinase inhibitors: the “Empower Me” Digital Therapeutic Study