Research Database

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.

Lung cancer is the leading cause of cancer death globally, primarily due to challenges in early detection. With funding from Stand Up to Cancer, LUNGevity Foundation, and the American Lung Association, a multidisciplinary team called the Lung Cancer Interception Dream Team was formed in 2017 to tackle this challenge, uniting expertise from various fields to enhance lung cancer interception and prevention. 

This initiative includes the development of a lung pre-cancer genome atlas (PCGA) aimed at understanding molecular changes linked to the progression of pre-cancerous lesions to lung carcinoma. With continued funding from LUNGevity Foundation and the American Lung Association, the team plans to establish a temporal atlas for premalignant lung adenocarcinoma by utilizing robot-assisted bronchoscopy to collect samples from patients with ground glass opacities (GGOs) suspected of lung cancer. This effort will not only help identify these lesions but also facilitate the targeted delivery of intervention agents. 

By gaining insights into progression-associated molecular alterations and cellular interactions, the team aims to significantly advance lung cancer interception strategies - catching cancer at its earliest stages and treatment it before it grows and spreads. Ultimately, the goal is to provide personalized interception approaches for individuals at risk of developing lung cancer.

This study will use data from the Veterans Affairs system to develop statistical models to predict response to immunotherapy in patients with lung cancer. While immunotherapy has improved outcomes for many patients, it is still not well understood why some respond well and others do not.  If successful, this work will produce a comprehensive prediction model of immunotherapy benefit in lung cancer that could be used to counsel patients, inform patient-physician decision making, and identify patients who need more- or less-aggressive treatment.

Dr. Florez will study the psychosocial and financial impact of lung cancer in young patients (< 50 years of age).  This patient population has seen an increase in incidence in recent years, but little is known about their specific needs.  The study will include administration of a survey and focus groups to understand unmet needs of this group of patients.  The information gathered from this study will be used to identify challenges unique to this population and develop the first clinical and research program of its kind for young lung cancer patients.

Around one in three patients with non-small cell lung cancer are diagnosed with early-stage disease, where surgery is offered as curative therapy. Unfortunately, the cancer can recur in 50%-60% of patients. The rate of recurrence is higher in patients whose tumors have certain mutations, such as mutations in the KRAS gene. Dr. Marrone and her team will be conducting a phase 2 trial to test whether treatment with a KRAS G12C blocking drug, adagrasib, given as a single drug or in combination with an immunotherapy drug, nivolumab, before a patient undergoes surgery can delay or prevent recurrence in patients whose tumors have a KRAS G12C mutation.

Alterations in the BRAF gene can lead to the development of non-small cell lung cancer. BRAF fusions are a type of BRAF gene alterations. These fusions are powerful growth stimulators of lung cancer. Currently, no treatment exists for cancers that harbor these BRAF fusions. Dr. Offin will be testing a series of new drugs in preclinical cell line and animal models of lung cancer. The ultimate goal of his project is to identify new drugs that can be tested in clinical trials.

In addition to tobacco use, having a previous malignancy is a risk factor for developing lung cancer. Head and neck cancer (HNC) survivors with a history of smoking have up to a 13% risk of developing lung cancer. Dr. Olazagasti’s study will assess the awareness and eligibility of lung cancer screening in Hispanic/LatinX HNC survivors via a survey questionnaire and understand the barriers to screening via qualitative interviews. The goal of her research is to create the first lung cancer screening program tailored for and focused exclusively on Hispanic/LatinX HNC survivors.

Osimertinib is the standard of care for treating non-small cell lung cancer with EGFR mutations. Unfortunately, the tumors inevitably develop resistance to osimertinib. Currently, very few treatment options exist for patients whose cancers have become resistant to osimertinib. Dr. Reuss is conducting a phase 2 clinical trial to test whether two immunotherapy drugs, atezolizumab and tiragolumab, given with a VEGF inhibitor, bevacizumab, are effective in controlling EGFR-positive NSCLC that has become resistant to osimertinib.

Recent studies have shown that high and low dose radiation used in combination with immunotherapy have a synergistic effect in modulating the growth of satellite tumors, which are tumor cells located near the primary tumor.  In this study, Dr. Shulman proposes using an animal model of metastatic lung cancer to test the hypothesis that radiation given in repeated very low dose pulses in combination with immunotherapy can further enhance immunotherapeutic benefit in metastatic lung cancer.

Dr. Velasquez Manana will conduct an observational study in a multiethnic group of patients with unresectable lung cancer to determine the association between social needs, care utilization, and quality of life.  The goal of this study is to fill a key knowledge gap in the care of patients with NSCLC and inform interventions to support patients at risk of social adversity during treatment to end disparities in lung cancer care.

Lymph nodes are small structures that work as filters for foreign substances, such as cancer cells and infections. These nodes contain infection-fighting immune cells that are carried in through the lymph fluid. This project will study the lymph node draining basin, which is involved in the spread of a tumor from the original location site to distant sites, and whether activating cancer-fighting T-cells can decrease recurrence in NSCLC.  Dr. Villena-Vargas will use animal models to investigate whether immune checkpoint inhibitors enhance lymph node T-cells memory, which increases their ability to recognize cancer cells in the bod and can prevent metastatic recurrence.

The purpose of this study is to develop and evaluate a method for personalized radiation therapy in patients with locally advanced NSCLC. Patients will be assessed regarding their expected risk of treatment toxicity, and those at lower risk will be treated in a fewer number of treatments with a more intensified dose of radiation. If successful, this could be used to inform optimal radiation treatment protocols as well as potentially reduce treatment and financial burden for patients, with a major impact on quality of life.

Currently available ALK inhibitors are an effective treatment for lung cancer, but tumors can development treatment resistance. In this project, Dr. Bivona will explore a novel way to treat ALK-positive lung cancer by targeting “membraneless cytoplasmic protein granules,” a new mechanism of signaling in ALK-positive lung cancer. His team will use precision medicine approaches that are complementary to current ALK inhibitors and that could improve their efficacy as well as quality of life for patients. 

In this project, Dr. Chiarle and his team will generate T cells that have engineered receptors, called TCR receptors (TCR-T cells), that will selectively target and attack the ALK protein that is expressed by tumor cells. Generation of such cells could be a powerful tool to eradicate ALK+ lung cancer cells and form the basis of a TCR-T cell-based clinical trial for patients with TKI-resistant ALK+ NSCLC.