Research Database

Immunotherapy has become a standard treatment regimen for advanced-stage non-small cell lung cancer. However, most patients do not respond. One significant barrier to immunotherapy efficacy is the tumor microenvironment (TME), which contains immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs). MDSCs represent an important tumor immune escape mechanism and play a role in the development and progression of lung cancer. Dr. Owen will be studying how this group of cells can be targeted to improve the effect of immunotherapy.

The use of mindfulness has the potential to address the multiple intersections of stigma in high-risk lung cancer groups inclusive of racial/ethnic and LGBTQ+ communities. A known approach of mindfulness (MOST) that has proven utility in other cancer-related fields has not been examined to a great extent in reducing stigma from lung cancer.

Dr. Riley is testing an innovative community-based participatory research (CBPR) and Multiphase Optimization Strategy (MOST) method to develop a brief virtual mindfulness intervention to decrease intersectional stigma. Dr. Riley will examine the reach, acceptability, and feasibility to underserved intersectional groups, including Black, Latinx, and LGBTQ+ lung cancer patients. This research project has a high likelihood of improving health behaviors and health outcomes for several communities.

The protein SGL2 seems to be produced in higher quantities on abnormal lung cells than on normal lung cells. Dr. Scafoglio is testing whether SGL2 can be used to image lung cancer cells by using a new imaging technology.

Fusion-driven NSCLC is a group of lung cancers that are driven by specific changes in oncogenes. These lung cancers tend to be addicted to these oncogenes. Such fusion-driven NSCLCs are treated with targeted therapies that block the effect of the oncogenes. However, the cancer inevitably comes back because the tumors become resistant. Traditionally, fusion-driven NSCLCs have not been successfully treated with immunotherapy. Dr. Schenk is testing how these cancers can be treated with immunotherapy through another immune pathway—the innate immunity pathway.

The lesbian, gay, bisexual, trans, and queer (LGBTQ) community faces several health disparities, including a higher rate of lung cancer due to increased rates of tobacco use in this group. Dr. Triplette will partner with an urban LGBTQ community center to create and evaluate a tailored lung cancer screening and smoking cessation navigation program to specifically address the needs of this community. By directly partnering with stakeholders and community members, he plans to develop a sustainable program that will assist LGBTQ community members with both screening and cessation that can then be disseminated to improve the health of LGBTQ patients across the country.

Currently, low-dose computed tomography (LDCT) is the only tool for the screening and early detection of lung cancer in individuals who meet screening criteria. LDCT is not very sensitive; often, abnormalities identified in an LDCT scan turn out to be benign. However, ruling out cancer requires an invasive biopsy. Dr. Vachani is testing whether a biomarker signature can be integrated into LDCT screening to improve the sensitivity of LDCT so that patients may be spared unnecessary biopsies.

Despite high tumor response rates, patients treated with EGFR targeted therapies, such as osimertinib, inevitably develop disease progression. Mechanisms of drug resistance remain incompletely understood on both a genomic and proteomic level. The objective of Dr. Lovly’s project is to find new targeted treatments and drug combinations that can tackle cancer evolution and osimertinib resistance.

As a mechanism of resistance to EGFR inhibitors, cancers can change histology from adenocarcinoma to small cell or squamous cell lung cancer. Once this happens, EGFR inhibitors are no longer effective treatment; there are no strategies currently available to prevent or reverse transformation after it has occurred. Dr. Yu will use advanced molecular techniques to identify genetic changes that contribute to transformation. Understanding these genetic changes will identify biomarkers that can be utilized to develop treatments to prevent and reverse transformation.

Dr. Arbour will test a combination treatment regimen (MRTX849 for KRAS G12C and TNO155 for SHP2) in specialized mouse models of KRAS-mutant lung cancer, as well as analyze blood samples from patients who are currently receiving the MRTX849 drug to proactively monitor how these patients are developing resistance to MRTX849. Her ultimate goal is for new drugs, such as TNO155, to be added to the treatment regimen for KRAS-positive patients to combat acquired resistance. Dr. Arbour is the recipient of the Kristie Rolke Smith/LUNGevity Career Development Award, generously funded by the Rolke family in memory of their daughter, Kristie.

Dr. Gay and his team will test an immunotherapy-DNA damage response (DDR) inhibitor combination therapy in SCLC patients and validate a biomarker profile. Dr. Gay’s research aims to develop a new drug therapy combination and determine which patients are likely to benefit from it. 

Dr. Pitroda and his team will develop a biomarker signature that can predict which patients are the most likely to benefit from an immunotherapy-radiation therapy combination. The ultimate goal is to determine which patients are likely to benefit from this combination treatment.

The lung cancer treatment landscape is rapidly evolving with the advent of immunotherapy. Now, three checkpoint inhibitors are available in the first-line and second-line settings for certain subsets of patients with advanced-stage NSCLC. Despite this promise, a large subset of patients treated with immunotherapy will not respond to these drugs. This lack of response may be attributed to immune suppressive mechanisms, such as interferon signaling.

Dr. Joshua Bauml’s laboratory is studying pathways that block interferon signaling, such as the JAK-STAT pathway. He proposes to conduct a phase II combination clinical trial (the immunotherapy drug pembrolizumab with the JAK-STAT pathway inhibitor itacitinib) in patients with advanced-stage NSCLC. Dr. Bauml postulates that the combination regimen will remove the immune suppressive effects of interferon signaling and enhance the action of pembrolizumab. He will also be collecting tumor and blood samples during the course of the trial and characterize these samples to identify molecular predictors of response in patients.