AACR-Johnson & Johnson Lung Cancer Innovation Science Grants

These grants represent a joint effort to address the need for promoting and supporting collaborative cancer research to bolster our understanding of how lung cancer can be successfully intercepted. Projects are implemented by multi-institutional teams composed of principal investigators from at least two, but no more than three, different institutions and include a clinical component with an endpoint relevant to improving the detection or treatment of lung cancer.

In 2019, priority was given to projects focused on the use of digital therapeutics and smoking cessation biomarkers/behavioral phenotyping for lung cancer interception.

2019 Grantees

Research
The team leaders previously demonstrated that electroencephalogram (EEG) assessment of reward sensitivity can be measured using neural responses associated with natural reward or smoking cues. These studies showed that low intrinsic reward sensitivity (IRS-) smokers are less likely to quit smoking than those high with intrinsic reward sensitivity (IRS+) and that varenicline offsets this deficit. Differences in reward sensitivity relate directly to activity in reward centers in the brain (striatum, dLPFC) and are associated with variation in the CHRNA3 rs578776 SNP. In this project, the team is set to extend their previous work by examining genetic correlates of reward sensitivity (IRS+/-) to select markers that previously predicted the IRS construct as well as those related to cessation, withdrawal, and medication response, and then validating this marker set on a prospectively collected sample of smokers.

Acknowledgement of Support
The AACR-Johnson & Johnson Lung Cancer Innovation Science Grant is important to our research program in smoking cessation because it will allow us to leverage nearly 800 existing genetic samples to predict reward sensitivity, validate this marker set on a subsequent prospective sample of smokers, and construct a custom chip that can be used by future scientists to identify the reward sensitivity construct.

Research
The primary goal of this study is to leverage digital technology to engage high-risk smokers in an innovative video-phone based smoking cessation program that introduces lung cancer screening as an option to enhance lung health. Efforts are underway to identify high-risk individuals through use of more precise methods such as risk prediction tools and/or genomic analyses to optimize the use of lung cancer screening technology. A secondary goal of this proposal is to gather information about smokers’ perceptions of lung cancer risk, their interest in actual receipt of calculated scores, and then the best way to present this information to enhance understanding.

Acknowledgement of Support
This award will allow our research team to combine our complementary skills to test an innovative intervention that seeks to engage high-risk smokers in behaviors that promote lung health, detect lung cancer sooner, and save more lives.

2018 Grantees

Research
The ability to assess changes in the early stages of lung adenocarcinoma development is extremely limited. The team hypothesizes that changes in the lung microenvironment promote selection and persistence of adaptive oncogenic events, indicating field cancerization even at sites remote from the malignant nodule. They are characterizing changes in clonal evolution, airway progenitor function, and the immune/inflammatory landscape in the peripheral lung field using brushings from individuals undergoing standard of care workup of CT-detected lung nodules.

Acknowledgement of Support
We want to thank the AACR and Johnson & Johnson for their generous support for our team project. This Lung Cancer Innovation Science Grant should facilitate a better understanding of how monitoring changes in peripheral lung tissue can help distinguish individuals at greatest risk of lung cancer and should enable the development of preventative interventions.

Research
The overall goal of this project is to examine relationships between antibodies to periodontal disease bacteria, peripheral blood immune profiles, and lung cancer risk. The team has been using existing banked pre-diagnostic bloods obtained at two different time points in the same individuals (CLUE I/II cohorts), in some cases up to 25 years prior to lung cancer diagnosis. They have been quantifying immune cell types in these archival samples using DNA methylation markers. Findings from this project can provide insight into the latency period between periodontal disease development and lung cancer incidence and inform on the nature of the etiological role of the immune response in lung cancer.

Acknowledgement of Support
The AACR-Johnson & Johnson Lung Cancer Innovation Science Grant will provide our multidisciplinary team with the funding necessary to address a number of novel and compelling hypotheses that will provide insight into immune alterations that occur many years prior to lung cancer diagnosis, potentially allowing for identification of new early detection biomarkers.

Research
There is growing evidence that the escape from immune surveillance plays a critical role in the progression from premalignancy to invasive lung cancer, as well as in postsurgical recurrence and that both the molecular landscape and microbiota can impact neoplastic progression and postsurgical recurrence. This project aims to comprehensively characterize the molecular, immune, and microbiome landscape of lung premalignancy as it evolves to early stage lung cancer and to assess the factors within this landscape that determine the postsurgical recurrence and response to immunotherapy.

Acknowledgement of Support
We sincerely appreciate the AACR and Johnson & Johnson for the 2018 Lung Cancer Innovation Science Grant to support our project, which we envision will provide novel insights for precise diagnosis, effective prevention, and treatment of lung cancers.