Research Database

Lung cancer is the leading cause of cancer deaths, with patients with EGFR-mutant NSCLC frequently developing brain metastases that are difficult to treat with existing therapies. Dr. Brea and his team are studying CAR-T cells that target TROP2, a protein commonly found on EGFR-mutant lung cancer cells. Targeting TROP2 can be diffficult because TROP2 is found on healthy cells.  To overcome this, Dr. Brea proposes two approaches:  (1) delivering CAR-T cells directly into the central nervous system (CNS). The CNS does not express TROP2 but is a site where tumors often reside, and (2) genetically editing the CAR-T cells to prevent them from entering healthy organs like lungs and gut. If successful in preclinical testing, this could provide a new targeted treatment option for patients with EGFR-mutant lung cancer with brain metastases.

Black Veterans face disproportionately higher rates of lung cancer diagnosis and death compared to other groups. Despite lung cancer screening (LCS) being life-saving through early detection, many Black Veterans remain unscreened due to low awareness, distrust of the VA system, and negative beliefs about lung cancer outcomes. This research aims to address these barriers by partnering with the National Association for Black Veterans (NABVETS) to co-design and test a community-based LCS awareness toolkit that can be distributed through trusted community organizations. 

Dr. Ogidigo will investigate how obesity affects lung cancer progression using a diet-induced obesity mouse model. She will focus on understanding how obesity-driven metabolic and chromatin changes influence lung tumor biology, and test incretin mimetics (metabolism-targeting drugs such as GLP1 agonists) as potential treatments to slow tumor growth in obesity models of lung cancer. By identifying obesity-specific molecular mechanisms and therapeutic targets, she aims to develop more effective, personalized treatment strategies for lung cancer patients with obesity or metabolic dysfunction.

While immunotherapy has significantly improved outcomes for non-small cell lung cancer (NSCLC), many patients still don't benefit from current treatments. Dr. Oh has developed a CCL21-DC vaccine that uses engineered dendritic cells (DCs) to display tumor mutations and train the immune system while producing CCL21 protein to attract more tumor-killing T cells. He has completed a clinical trial combining this vaccine with pembrolizumab immunotherapy in patients with NSCLC, and collected tumor biopsies and blood samples before and after treatment. Using advanced sequencing techniques on these samples, he aims to understand how the vaccine affects tumor-targeting T cells and their interactions within tumors. These studies will guide future improvements in DC vaccines and other immunotherapies for lung cancer patients.

EGFR gene alterations are found in 15%-30% of lung adenocarcinomas (LUADs). While EGFR-targeted therapies are initially effective, most patients eventually relapse due to treatment resistance. Recent research has identified "persister cells" - tumor cells that survive throughout targeted treatment and are believed to be a primary cause of cancer recurrence in EGFR-mutant LUAD. This project aims to understand how these persister cells survive despite targeted therapy and identify ways to eliminate them. The ultimate goal is to identify resistance factors, develop therapeutic strategies to eradicate persister cells, and provide the scientific foundation for clinical trials to improve outcomes for patients with EGFR-mutant LUAD. 

Lung cancer is the leading cause of cancer deaths globally. While immunotherapy has improved survival rates, many tumors don't respond due to mutations that can lead to poor treatment outcomes. In this project, Dr. Woodard will investigate how T cells are prevented from entering tumors with specific mutations and explore ways to enhance T cell migration to improve immunotherapy response. She will focus on PLA2G10, a protein that blocks T cell entry into lung tumors, examining how it prevents CD4+ and CD8+ T cell migration and its relationship with common lung cancer mutations. The goal is to understand and improve T cell exclusion mechanisms to make immunotherapy more effective. 

Dr. Grippin will investigate how mRNA vaccines can be combined with radiation therapy to improve lung cancer treatment outcomes. Preliminary data shows that NSCLC patients who received mRNA vaccines alongside radiation and immune checkpoint inhibitors had better survival rates. The study aims to optimize this combination therapy to overcome resistance in immune-refractory lung cancer as well as develop enhanced mRNA vaccine formulations. The findings will provide additional data for clinical trials integrating mRNA vaccines into standard lung cancer care, potentially making immunotherapy more effective.

Dr. Deutsch’s proposal centers around finding better pathologic predictors of response to neoadjuvant IO in early stage NSCLC.  She will utilize machine learning/artificial intelligence to test an algorithm that she and her team have developed that assesses percent residual viable tumor (%RVT), which is the amount of tumor left at the time of surgery.  Dr. Deutsch will also characterize tissue specimens using a novel immunofluorescence platform to identify cell types and spatial relationships that are associated with patient benefit to immunotherapy+chemotherapy.  This approach can help inform which patients should receive a given therapy, how they will respond, and additional possible targets for the development of new therapies.

The introduction of targeted therapies and immunotherapy for early-stage lung cancer is associated with improved survival, but patients can only benefit if they partake in adjuvant and neoadjuvant therapies.  Data has shown that inequalities exist for patients with lower socioeconomic status as well as non-White patients when it comes to being referred for and receiving treatment after surgery.  These inequalities are likely to increase as new drugs are developed in clinical trials comprised of predominantly white patients.  In this project, Dr. Nobel will study the impact of disparities on uptake of adjuvant therapy for NSCLC in a largely minority patient population at Montefiore Medical Center in Bronx, NY.  She will provide social support and health literacy to engage patients in their care and collect genetic data about their tumors, which will contribute to future clinical trials that are more inclusive.

In patients with EGFR-mutant NSCLC, tyrosine kinase inhibitors (TKIs) have been an effective treatment, but over time these patients develop resistance to TKIs, leading to tumor relapse.  Dr. Yang’s project focuses on cancer cells called drug-tolerant persisters (DTPs), which are implicated in TKI resistance.  A gene called HER3 is expressed in DTPs, and Dr. Yang will use specially engineered immune cells, called CAR-T cells, to target both HER3 and EGFR simultaneously.  If successful, this approach would result in a bi-specific CAR-T cell that can be further evaluated in clinical trials.

This project will investigate the role of cells called macrophages, key components of the immune system that have multiple functions, including immune surveillance within a unique communication pathway called hedgehog (Hh). The hedgehog signaling pathway is involved in cell growth and differentiation, as well as maintenance of stem cells and tissue repair. Disruption or inhibition of Hh can create an environment that is less favorable for survival of cancer cells, allowing a patient’s immune system to combat it more effectively.  This research has the potential to benefit patients who have been diagnosed with NSCLC, who have not responded to current treatments including immunotherapy by boosting the body’s own defense mechanisms.

This project will investigate novel protein degraders (called PROTACs) as a treatment for RET-positive cancers, and will evaluate their efficacy in vitro and in vivo in prostate and lung cancer. PROTACs are highly specific molecules that degrade unwanted or harmful proteins in cells (in this case, RET tyrosine kinase). This research aims to provide a novel therapeutic approach targeting RET signaling, which could overcome resistance to existing RET inhibitors.  If successful, it would be a first-in-class compound for further clinical development.

The objective of this project is to develop a blood test that can improve upon current limitations in lung cancer screening.  Dr. Patel and his team have developed a method to accurately measure alterations in DNA that are cancer-specific by looking at levels of methylation of circulating tumor DNA (ctDNA) in the bloodstream.  Using this method, Dr. Patel will develop a predictive model to identify patients with lung cancer based on these DNA alterations at a single time point, as well as an algorithm that can track these changes in a patient’s DNA over time.  If successful, this could help detect lung cancer earlier in its development, thereby leading to better outcomes for patients.

This project will explore the use of neoantigens to evaluate immunogenic priming of dendritic cells (DC) in RET+ NSCLC.  Neoantigens are short protein fragments present only in cancer cells that bind to genetically encoded proteins known as human leukocyte antigens (HLA).  Dr. Cummings will use features of HLA to predict which cancer-specific protein fragments best match an individual’s immune system, utilizing a biobank of RET-rearranged NSCLC biospecimens. This approach could help identify optimal immunogenic targets, that could be translated into a pathway for clinical use of personalized DC vaccines.

This project aims to develop new therapeutic approaches for RET-positive cancers, focusing on overcoming resistance to currently available RET inhibitors.  Dr. Somwar and colleagues will investigate ways to block the growth of lung cancers with altered RET in a pathway called MAPK (mitogen activated kinase), which is involved in many biological processes involving cell growth and survival.  MAPK is implicated in developing resistance to RET inhibitors and finding strategies to target this pathway in combination with RET could benefit many patients who have no approved therapy options after tumor reoccurence. 

Dr. Benjamin’s research focuses on improving the rates of lung cancer screening. Currently, there is interest in “centralizing” lung cancer screening into self-contained programs or one-stop shops, with dedicated support staff and clinical personnel to coordinate shared decision-making, scheduling imaging, and arranging appropriate follow-up care. However, it is poorly understood how these centralized programs compare to “decentralized” screening that is coordinated by primary care physicians directly with their patients. Dr. Benjamin seeks to utilize nationwide longitudinal data from multiple lung cancer screening programs from the Veterans Affairs Healthcare System to evaluate and compare the performance of centralized versus decentralized screening programs, with particular focus on highlighting their effectiveness within various racial and income groups.

This project proposes to develop novel therapeutic approaches to treat advanced EGFR-mutant NSCLC. CAR-T cell therapy is a type of immunotherapy treatment that uses genetically altered T cells to find and destroy cancer cells more effectively.  TROP2 is a protein that is over expressed on the surface of NSCLC and is a target of the antibody-drug conjugate (ADC), sacitizumab-govitecan, which is FDA-approved to treat other solid tumors. Dr. Brea hypothesizes that TROP2-directed CAR-T targeting of EGFR-mutant NSCLC will be superior to standard Osimertinib treatment.

Small cell lung cancer (SCLC) is difficult to treat, and most patients diagnosed have a poor prognosis. Most patients with SCLC treated with first line chemoimmunotherapy progress within months of immune checkpoint inhibitor (ICI) maintenance therapy. Previous studies in mice have revealed that SCLC treated with iadademstat and maintenance ICI shows enhanced tumor response compared to ICI alone. Dr. Choudhury will conduct a phase II randomized trial investigating this combination in patients with SCLC versus standard of care ICI alone to evaluate progression free survival.

Lung cancer is the number one cause of cancer-related deaths in the US because it is often found only after it has spread to other organs in the body, decreasing the likelihood of surviving at least 5 years after diagnosis.  Only 21% of patients are diagnosed then their lung cancer is early stage, when it is most treatable.  The goal of this project is to create a new way to screen for lung cancer using a blood sample that can find early stage disease when patients can still be treated and/or cured.  In preliminary work, Dr. Diehn has developed a blood test that can identify tiny amounts of DNA from lung cancer cells and in this study he will improve this test and apply it to patients and healthy controls.  If successful, Dr. Diehn’s work has the potential to significantly improve early detection of lung cancer and improve outcomes for patients.

Although the average age at diagnosis is 70, thousands of new patients under 45 are diagnosed with lung cancer every year, most of whom have never smoked.  Dr. LoPiccolo hypothesizes that these patients may share inherited genetic changes that predispose them to developing lung cancer at a younger age.  In a preliminary analysis of young-onset lung cancer patients, Dr. LoPiccolo has found that approximately 30% of these patients carry rare mutations in known cancer-associated genes.  In this study, Dr. LoPiccolo will investigate whether these mutations affect response to targeted or immune-based therapies.  This insight is likely to identify risk factors among young lung cancer patients, which could lead to improved screening and treatment options for this population.