Research Database

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.

The veteran population is disproportionately affected by lung cancer and relatively few patients that are eligible participate in lung cancer screening. This low participation is due to barriers such as provider bias, structural racism, patient mistrust, and fear of diagnosis. In this project, Dr. Navuluri proposes to develop and test an electronic shared decision-making aid and referral tool to improve equity in lung cancer screening (LCS).  She will pilot test the aid to assess its feasibility and usability among patients and providers within the Durham VA system.

Dr. Ocadiz Ruiz proposes to develop a bioengineered scaffolding and test it in mouse models.  If successful, this research could progress to a phase 1 clinical trial and lay the groundwork for a new technology to be used in individuals with increased risk of lung cancer. This technology has to potential to make biopsies and consequently, early detection, easier.

In this project, Dr. Trovero will study the role of METTL3, an RNA modifying protein that is thought to promote tumor initiation and progression.   She will evaluate the function of METTL3 by increasing or decreasing its activity in vivo.  Results from this study will help establish METTL3 as a possible therapeutic target for lung cancer, and pave the way for understanding the relationship between RNA modifiers and cancer biology.

Checkpoint immunotherapy has advanced treatment of NSCLC, but the majority of patients do not experience long-term disease control and are at risk for autoimmune-related side effects.  In this study, Dr. Tseng will examine specialized cells called CD8+ T that express receptors (KIR+) that suppress autoimmunity to understand how these cells regulate the immune system’s cancer-fighting ability during checkpoint immunotherapy treatment.  Insights gained from this study could result in better strategies for improving efficacy while decreasing immune-related side effects.

Radiation therapy remains a cornerstone treatment for patients with locally advanced lung cancer, however knowing which patients will respond and which will not respond is still poorly understood.  The goal of this project is to analyze genomic and radiomic data from patients with NSCLC to understand how tumors change during therapy and create models to predict therapeutic response that will assist with clinical decision making.

Tyrosine kinase inhibitors (TKI) are a class of drugs that are used to treat EGFR NSCLC. These drugs eventually stop working and some cancer cells called drug-tolerant persisters (DTPs) are implicated in this resistance.  Dr. Kobayashi and his team have found that a protein called CD74 plays a role in developing a resistance to osimertinib.  In this project, he will investigate whether CD74-expressing cells allow for the development of DTPs and if inhibition of CD74 by combining an antibody-drug conjugate (CD74-MMAE) with osimertinib, prevents resistance. If successful, this has the potential to significantly impact the survival of EGFR patients by allowing them to stay on osimertinib for a longer duration.

In this project, Dr. Reuben and colleagues aim to develop a novel therapeutic strategy harnessing immune response in EGFR-mutant NSCLC.  He will use engineered T cells with receptors targeting EGFR antigens to eradicate drug-tolerant persister (DTP) cells, preventing the emergence of resistance following treatment by osimertinib.  This work lays the foundation for use of TCR-engineered T cells in treating patients with EGFR mutations.