Medicine and Health Sciences Commons^™

Hypermetabolic Lymphadenopathy Following The Administration Of Covid-19 Vaccine And Immunotherapy In A Lung Cancer Patient: A Case Report, Shreya Tripathy, Nathaniel Alvarez, Shubham Jaiswal, Ryan Williams, Munaf Al-Khadimi, Sarah Hackman, William Phillips, Supreet Kaur, Sherri Cervantez, William Kelly, Josephine Taverna

Research Symposium

Background: Given the current climate of the pandemic, lung cancer patients are especially vulnerable to complications from severe acute respiratory syndrome coronavirus 2 infection. As a high-risk population group, these patients are strongly advised to receive coronavirus disease 2019 vaccination in accordance with Center for Disease Control and Prevention guidelines to minimize morbidity and mortality. In recent years, immunotherapy has taken a preeminent role in the treatment of non-small cell lung cancer with dramatic improvement in overall survival. Reactive lymphadenopathy following the administration of a coronavirus disease 2019 vaccination can confound the radiographic interpretation of positron emission tomography-computed tomography or …

Temporal Considerations In Brain Metastases Radiation Therapy: The Intersection Of Chronobiology And Patient Profiles, Nicolas Nelson, Sara Burke, Louis Cappelli, Lauren Matlack, Alexandria Smith, Noelle Francois, Joseph Lombardo, Yash Shah, Kuang-Yi Wen, Ayesha A Shafi, Nicole Simone

Department of Radiation Oncology Faculty Papers

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing’s impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival …

Individual- And Neighborhood-Level Characteristics Of Lung Cancer Screening Participants Undergoing Telemedicine Shared Decision Making, Christine S. Shusted, Hee-Soon Juon, Brooke Ruane, Brian M. Till, Charnita Zeigler-Johnson, Russell K. Mcintire, Tyler Grenda, Olugbenga Okusanya, Nathaniel R. Evans, Gregory C. Kane, Julie Barta

Division of Pulmonary and Critical Care Medicine Faculty Papers

BACKGROUND: Although lung cancer screening (LCS) for high-risk individuals reduces lung cancer mortality in clinical trial settings, many questions remain about how to implement high-quality LCS in real-world programs. With the increasing use of telemedicine in healthcare, studies examining this approach in the context of LCS are urgently needed. We aimed to identify sociodemographic and other factors associated with screening completion among individuals undergoing telemedicine Shared Decision Making (SDM) for LCS.

METHODS: This retrospective study examined patients who completed Shared Decision Making (SDM) via telemedicine between May 4, 2020 - March 18, 2021 in a centralized LCS program. Individuals were …

From The Lung To The Finger: An Unusual Presentation Of Adenosquamous Cell Carcinoma, Preeti Badve, Md, Sussy Obando Lara, Md, Elisenda Valdez Pena, Md, Myriah Magaris, Do, Zunaira Naeem, Md, Charalambos Solomides, Md, Avnish Bhatia

Department of Medical Oncology Posters

Learning Objective

To recognize unusual presentations of metastatic lung disease.

A Unique Case Of Atrial Fibrillation Secondary To Squamous Cell Lung Carcinoma, Mohammad J. Malik, Emily K. Wilson, Vijay Bandhakavi

Research Day

Atrial fibrillation (AF) is widely considered to be the most prevalent cardiac arrhythmia with an incidence of roughly 1-2% in the United States alone. The incidence of AF has been known to increase with advancing age and thus presents a significant burden on healthcare systems across the globe. AF arises as a result of several mechanisms including structural changes that occur to the heart overtime. Here we present a case in which a 63-year-old male with no past medical history except heavy tobacco use presented to the emergency department complaining of shortness of breath. He also endorsed having palpitations and …

Social Determinants Of Health Among Family Caregiver Centered Outcomes In Lung Cancer: A Systematic Review, Dede K. Teteh, Madeleine Love, Marissa Ericson, Marissa Chan, Tanyanika Phillips, Aroona Toor, Betty Ferrell, Loretta Erhunmwunsee, Susanne B. Montgomery, Virginia Sun, Jae Y. Kim

Health Sciences and Kinesiology Faculty Articles

Background: Lung cancer is the leading cause of cancer death globally. Both lung cancer patients and family caregivers (FCGs) have unmet quality of life (QOL) needs. An understudied topic in lung cancer research is the role of social determinants of health (SDOH) on QOL outcomes for this population. The purpose of this review was to explore the state of research on SDOH FCGs centered outcomes in lung cancer.

Methods: The databases PubMed/MEDLINE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and American Psychological Association (APA) PsycInfo were searched for peer-reviewed manuscripts evaluating defined SDOH domains on …

Met Alterations Are Associated With Osimertinib Resistance In Egfr Mutant Lung Cancers, A Meta-Analysis, Annie Le, Marissa Viola, Jun Wang

Research Day

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) that has been used to treat EGFR mutant lung cancers, especially those with EGFR T790M mutation. Resistance to osimertinib is likely associated with acquired genetic alterations in these cancer cells. Mesenchymal epithelial transition (MET) is a tyrosine kinase and its amplification is frequently seen in osimertinib resistant patients. To investigate whether the presence of MET alteration is associated with osimertinib resistance, a meta-analysis was conducted using published observations of EGFR mutant lung cancer patients treated with osimertinib. Frequencies of MET alterations are variable, ranging from 0-43% in osimertinib resistant patients. MET alteration …

Mir-218-5p/Egfr Signaling In Arsenic-Induced Carcinogenesis, Ranakul Islam, Lei Zhao, Xiujuan Zhang, Ling-Zhi Liu

Department of Medical Oncology Faculty Papers

Background: Arsenic is a well-known carcinogen inducing lung, skin, bladder, and liver cancer. Abnormal epidermal growth factor receptor (EGFR) expression is common in lung cancer; it is involved in cancer initiation, development, metastasis, and treatment resistance. However, the underlying mechanism for arsenic-inducing EGFR upregulation remains unclear.

Methods: RT-PCR and immunoblotting assays were used to detect the levels of miR-218-5p and EGFR expression. The Luciferase assay was used to test the transcriptional activity of EGFR mediated by miR-218-5p. Cell proliferation, colony formation, wound healing, migration assays, tube formation assays, and tumor growth assays were used to study the function of miR-218-5p/EGFR …

Spontaneous Large Volume Hemothorax Managed With A Small-Bore Chest Tube, Moiz Salahuddin, Samia Ayub

Department of Medicine

A 67-year-old male with metastatic lung cancer presented with acute shortness of breath and increasing oxygen requirements. He had a decreasing hemoglobin for which he required red blood cell transfusions. His chest x-ray showed near complete white-out of the left lung. Bedside ultrasound (Handheld Sonostar C4PL) showed a large pleural effusion with swirling echogenic material suggestive of plankton sign. The pleural effusion was aspirated and showed frank blood, after which a small-bore chest tube (SBCT) was inserted. A total of 3200ml of blood was drained with the SBCT. There was complete clearance of the pleural space, and no further blood …

Idiopathic Pulmonary Fibrosis And Lung Cancer: Future Directions And Challenges, Ahmad Abu Qubo, Jamil Numan, Juan Snijder, Maria Padilla, John H.M. Austin, Kathleen M. Capaccione, Monica Pernia, Jean Bustamante, Timothy O’Connor, Mary M. Salvatore

Einstein Health Papers

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of pulmonary scarring. New treatments slow disease progression and allow pulmonary fibrosis patients to live longer. Persistent pulmonary fibrosis increases a patient’s risk of developing lung cancer. Lung cancer in patients with IPF differs from cancers that develop in the non-fibrotic lung. Peripherally located adenocarcinoma is the most frequent cell type in smokers who develop lung cancer, while squamous cell carcinoma is the most frequent in pulmonary fibrosis. Increased fibroblast foci in IPF are associated with more aggressive cancer behaviour and shorter doubling times. Treatment of lung cancer in fibrosis is challenging …

Lymph Node Dissections And Survival In Sublobar Resection Of Non-Small Cell Lung Cancer ≤ 20 Mm., Shinkichi Takamori, Takefumi Komiya Md, Mototsugu Shimokawa, Emily Powell Phd

PCI Publications and Projects

BACKGROUND: A randomized trial of lobectomy versus segmentectomy for small-sized (≤ 20 mm) non-small cell lung cancer (NSCLC) showed that patients who had undergone segmentectomy had a significantly longer overall survival (OS) than those who had lobectomy. More attention is needed regarding the required extent of thoracic lymphadenectomy in patients with small-sized NSCLC who undergo sublobar resection.

METHODS: The National Cancer Database was queried for patients with clinically node-negative NSCLC ≤ 20 mm who had undergone sublobar resection between 2004 and 2017. OS of NSCLC patients by the number of lymph node dissections (LNDs) was analyzed using log-rank tests and …

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer., Richard Fu

Poster Presentations

Honors thesis poster presentation.

RAS, one of the most prevalent oncogenes, is mutated in 27% of human cancers. Gainof- function RAS mutations activate multiple downstream pathways, including the RASRAF- MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. The RAS proteins KRAS, HRAS, and NRAS along with their downstream effectors are attractive targets for cancer therapy since they act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named …

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu

Undergraduate Honors Theses

RAS is a prevalent oncogene that is mutated in 27% of human cancers. Gain-of-function RAS mutations activate multiple downstream pathways, including the RAS-RAF-MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. RAS proteins such as KRAS, a member of the RAS protein family, and their downstream effectors are attractive targets for cancer therapy since their mutations act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named MCI-062 was …

Concurrent P53 Mutation In Egfr Mutant Non-Small Cell Lung Cancer Is Associated With Resistance To First And Second Generation Egfr Tyrosine Kinase Inhibitors, A Meta-Analysis, Marissa Viola, Adam Kolatorowicz, Jun Wang

Research Day

Epidermal growth factor receptor (EGFR) mutant lung cancers tend to respond well to EGFR tyrosine kinase inhibitors (TKIs). However, resistance has been described. Molecular studies have revealed that concurrent mutations of tumor driver genes are associated with TKI resistance. To delineate the role of concurrent mutation of tumor suppressor gene p53 in TKI resistance, a meta-analysis was performed using published observations of EGFR mutant lung cancer patients treated with first or second generation TKIs. 31 studies are included in the analysis following a search of PubMed. Probability of TKI resistance and progress free survival (PFS) were compared in patients with …

Developing Novel Water-Soluble Porphyrins For Potential Use As Photosensitizers In Photodynamic Therapy, Kayla R. Whittington

Honors Theses

Photodynamic therapy (PDT) is a treatment modality for various illnesses, including some types of cancer. Lung cancer is the leading cause of cancer death in the United States. The prevalence of lung cancer in certain gender, racial, ethnic, and socioeconomic groups add to existing health disparities in the United States. For this reason, it is necessary to address the social determinants underlying lung cancer disparities, as well as improve treatment options. These treatment options should be cost effective, convenient, and increase survival rates. This research focused on synthesizing novel water-soluble porphyrin compounds for use as photosensitive agents in PDT for …

Landscape Of Molecular Crosstalk Perturbation Between Lung Cancer And Covid-19, Aditi Kuchi, Jiande Wu, Jyotsna Fuloria, Chindo Hicks

School of Medicine Faculty Publications

Background: Lung cancer patients have the worst outcomes when affected by coronavirus disease 2019 (COVID-19). The molecular mechanisms underlying the association between lung cancer and COVID-19 remain unknown. The objective of this investigation was to determine whether there is crosstalk in molecular perturbation between COVID-19 and lung cancer, and to identify a molecular signature, molecular networks and signaling pathways shared by the two diseases. Methods: We analyzed publicly available gene expression data from 52 severely affected COVID-19 human lung samples, 594 lung tumor samples and 54 normal disease-free lung samples. We performed network and pathways analysis to identify molecular networks …

Human Endothelial Cells Promote Arsenic-Transformed Lung Epithelial Cells To Induce Tumor Growth And Angiogenesis Through Interleukin-8 Induction, Lei Zhao, Yi-Fang Wang, Jie Liu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated. In this study, we found that endothelial cells significantly increased As-T cell-induced tumor growth compared to those induced by As-T cells alone. To understand the molecular mechanism, we found that endothelial cells co-cultured with As-T cells or cultured in conditioned medium (CM) prepared from As-T cells showed much higher cell migration, proliferation, and tube formation compared to those co-cultured with BEAS-2B …

Integration Of Liquid Biopsy And Pharmacogenomics For Precision Therapy Of Egfr Mutant And Resistant Lung Cancers, Jill M. Kolesar, Spencer Peh, Levin Thomas, Gayathri Baburaj, Nayonika Mukherjee, Raveena Kantamneni, Shirley Lewis, Ananth Pai, Karthik S. Udupa, Naveena Kumar An, Vivek M. Rangnekar, Mahadev Rao

Pharmacy Practice and Science Faculty Publications

The advent of molecular profiling has revolutionized the treatment of lung cancer by comprehensively delineating the genomic landscape of the epidermal growth factor receptor (EGFR) gene. Drug resistance caused by EGFR mutations and genetic polymorphisms of drug metabolizing enzymes and transporters impedes effective treatment of EGFR mutant and resistant lung cancer. This review appraises current literature, opportunities, and challenges associated with liquid biopsy and pharmacogenomic (PGx) testing as precision therapy tools in the management of EGFR mutant and resistant lung cancers. Liquid biopsy could play a potential role in selection of precise tyrosine kinase inhibitor (TKI) therapies during different phases …

Multi-Modality Automatic Lung Tumor Segmentation Method Using Deep Learning And Radiomics, Siqiu Wang

Theses and Dissertations

Delineation of the tumor volume is the initial and fundamental step in the radiotherapy planning process. The current clinical practice of manual delineation is time-consuming and suffers from observer variability. This work seeks to develop an effective automatic framework to produce clinically usable lung tumor segmentations. First, to facilitate the development and validation of our methodology, an expansive database of planning CTs, diagnostic PETs, and manual tumor segmentations was curated, and an image registration and preprocessing pipeline was established. Then a deep learning neural network was constructed and optimized to utilize dual-modality PET and CT images for lung tumor segmentation. …

Analyzing The Relationship Between The Quality Of Life And Race Of Lung Cancer Survivors, Alina S. Wise

Honors Undergraduate Theses

Purpose: The relationship between racial disparities and the health-related quality of life (HRQoL) of lung cancer patients is not well understood. The purpose of this study was to quantify the overall HRQoL of lung cancer patients and compare differences in HRQoL among racial groups in the United States.

Methods: We analyzed data from the Behavioral Risk Factors Surveillance System (BRFSS), a population-based national cross-sectional study conducted by the Centers for Disease Control and Prevention. The BRFSS is conducted annually in all 50 states and collects information on demographics, health behaviors, health-related experiences, health conditions, use of medications, and use of …

Lung Cancer Screening: An Evidence-Based Practice Change Project, Robert Bland

Student Scholarly Projects

Practice Problem: Lung cancer is the leading cause of global cancer deaths and is a significant health issue in the US, claiming more than 155,000 lives each year. Lung cancer screening through low dose computed tomography (LDCT) can reduce lung cancer mortality by 20 percent but unfortunately, lung cancer screening is underutilized.

PICOT Question: The PICOT question that guided this project was: in a patient population eligible for LDCT lung screening (P), how does auditing of practice with feedback to the providers (I), compared to not doing the interventions as mentioned above (C), increase LDCT lung cancer screenings in the …

Engaging Patients With Late-Stage Non-Small Cell Lung Cancer In Shared Decision Making About Treatment, Ronald E. Myers, Shailesh M. Advani, Pamela Myers, Preethi Selvan, Gregory Garber, Brooke Worster, Neal Flomenberg, Andrew Chapman, Ralph Zinner

Internal Medicine Faculty Publications

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. …

Diagnosis-To-Surgery Interval And Survival For Different Histologies Of Stage I-Iia Lung Cancer, Lu Zhang, Mei Chin Hsieh, Lior Rennert, Paige Neroda, Xiao Cheng Wu, Chindo Hicks, Jiande Wu, Ronald Gimbel

School of Medicine Faculty Publications

Background: Guidelines on timeliness of lung cancer surgery are inconsistent. Lung cancer histologic subtypes have different prognosis and treatment. It is important to understand the consequences of delayed surgery for each lung cancer histologic subtype. This study aimed to examine the association between diagnosis-to-surgery time interval and survival for early stage lung cancer and selected histologic subtypes. Methods: Patients diagnosed with stage I-IIA lung cancer between 2004 and 2015 receiving definitive surgery and being followed up until Dec. 31, 2018, were identified from Surveillance, Epidemiology, and End Results database. Histologic subtypes included adenocarcinoma, squamous or epidermoid carcinoma, bronchioloalveolar carcinoma, large …

Pembrolizumab Plus Concurrent Chemoradiation Therapy In Patients With Unresectable, Locally Advanced, Stage Iii Non-Small Cell Lung Cancer: The Phase 2 Keynote-799 Nonrandomized Trial., Salma K Jabbour, Ki Hyeong Lee, Nikolaj Frost, Valeriy Breder, Dariusz M Kowalski, Theodore Pollock, Evgeny Levchenko, Noemi Reguart, Alex Martinez-Marti, Baerin Houghton, Jean-Baptiste Paoli, Sufia Safina, Keunchil Park, Takefumi Komiya Md, Amy Sanford, Vishal Boolell, Hong Liu, Ayman Samkari, Steven M Keller, Martin Reck

PCI Publications and Projects

IMPORTANCE: Administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non-small cell lung cancer (NSCLC).

OBJECTIVE: To evaluate treatment outcomes and safety of pembrolizumab plus cCRT in stage III NSCLC.

DESIGN, SETTING, AND PARTICIPANTS: The phase 2, nonrandomized, 2-cohort, open-label KEYNOTE-799 study enrolled patients between November 5, 2018, and July 31, 2020, from 52 academic facilities and community-based institutions across 10 countries. As of October 28, 2020, median (range) follow-up was 18.5 (13.6-23.8) months in cohort A and 13.7 (2.9-23.5) months in cohort B. Of 301 patients screened, 216 eligible …

Role Of Immunotherapy In Stage Iv Large Cell Neuroendocrine Carcinoma Of The Lung., Takefumi Komiya Md, Neema Ravindra, Emily Powell Phd

PCI Publications and Projects

BACKGROUND: Despite approvals of immune checkpoint inhibitors in both small cell and non-small cell lung cancers, the role of immunotherapy in large cell neuroendocrine carcinoma (LCNEC) in lung is undefined.

METHODS: Using the National Cancer Database (NCDB), Stage IV lung LCNEC cases diagnosed from 2014 to 2016 were analyzed. Information regarding cancer treatment was limited to first course of therapy, including surgery for primary lesion, radiation, chemotherapy, and immunotherapy. Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analysis.

RESULTS: Among 661 eligible cases, 37 patients were treated with immunotherapy. No …

Community Health Interventions To Reduce The Burden Of Radon-Related Lung Cancer, Benjamin Weaver

Family Medicine Clerkship Student Projects

Exposure to radon is the second leading cause of lung cancer in the United States. One in seven homes in Vermont has elevated levels of radon, but most patients are unaware of radon as a risk factor for lung cancer or that radon testing and mitigation services are available to them. To promote increased testing and mitigation of radon we screened patients presenting to a Family Medicine practice in Vermont about whether they had had these services done in their home. We also developed a patient education resource for providers to give to patients who had more questions about radon …

A New Efficient Method To Detect Genetic Interactions For Lung Cancer Gwas, Jennifer Luyapan, Xuemei Ji, Siting Li, Xiangjun Xiao, Dakai Zhu, Eric J. Duell, David C. Christiani, Matthew B. Schabath, Susanne M. Arnold, Shanbeh Zienolddiny, Hans Brunnström, Olle Melander, Mark D. Thornquist, Todd A. Mackenzie, Christopher I. Amos, Jiang Gui

Markey Cancer Center Faculty Publications

BACKGROUND: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of …

A Lung Cancer Screening Personalized Decision-Aid Improves Knowledge And Reduces Decisional Conflict Among A Diverse Population Of Smokers At An Urban Academic Medical Center, Madeline Kaufman, Nilan Schnure, Andrea Nicholson, Frank Leone, Carmen Guerra

Journal of Health Disparities Research and Practice

Introduction: Few lung cancer screening decision aids have been tested in diverse populations. The study objective was to determine whether the online decision aid www.shouldiscreen.com impacts knowledge of and decisional conflict around lung cancer screening in a diverse population.

Methods: Eligible patients had significant smoking histories, were at increased risk for lung cancer (ages 45-80, >20 pack-years, smoking within last 15 years) and had no history of prior lung cancer or screening. Data was collected and analyzed in 2017.

Results: 40 patients were enrolled: 80% were female, 62.5% black, 33% white, and 48% had a high school …

Palbociclib Treatment Alters Nucleotide Biosynthesis And Glutamine Dependency In A549 Cells, Lindsey R. Conroy, Pawel Lorkiewicz, Liqing He, Xinmin Yin, Xiang Zhang, Shesh N. Rai, Brian F. Clem

Neuroscience Faculty Publications

Background

Aberrant activity of cell cycle proteins is one of the key somatic events in non-small cell lung cancer (NSCLC) pathogenesis. In most NSCLC cases, the retinoblastoma protein tumor suppressor (RB) becomes inactivated via constitutive phosphorylation by cyclin dependent kinase (CDK) 4/6, leading to uncontrolled cell proliferation. Palbociclib, a small molecule inhibitor of CDK4/6, has shown anti-tumor activity in vitro and in vivo, with recent studies demonstrating a functional role for palbociclib in reprogramming cellular metabolism. While palbociclib has shown efficacy in preclinical models of NSCLC, the metabolic consequences of CDK4/6 inhibition in this context are largely unknown.

Methods

In …

Immune-Mediated Genetic Pathways Resulting In Pulmonary Function Impairment Increase Lung Cancer Susceptibility, Linda Kachuri, Mattias Johansson, Sara R. Rashkin, Rebecca E. Graff, Yohan Bossé, Venkata Manem, Neil E. Caporaso, Maria Teresa Landi, David C. Christiani, Paolo Vineis, Geoffrey Liu, Ghislaine Scelo, David Zaridze, Sanjay S Shete, Demetrius Albanes, Melinda C. Aldrich, Adonina Tardón, Gad Rennert, Chu Chen, Gary E. Goodman, Jennifer A. Doherty, Heike Bickeböller, John K. Field, Michael P Davies, M. Dawn Teare, Lambertus A. Kiemeney, Stig E. Bojesen, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Loïc Le Marchand, Iona Cheng, Matthew B. Schabath, Eric J. Duell, Angeline S. Andrew, Jonas Manjer, Philip Lazarus, Susanne M. Arnold, James D. Mckay, Nima C. Emami, Matthew T. Warkentin, Yonathan Brhane, Ma'en Obeidat, Richard M. Martin, Caroline Relton, George Davey Smith, Philip C. Haycock, Christopher I. Amos, Paul Brennan, John S. Witte, Rayjean J. Hung

Markey Cancer Center Faculty Publications

Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV₁: r_g = 0.098, p = 2.3 × 10^-8) and the ratio of FEV₁ to forced vital capacity (FEV₁/FVC: r_g = 0.137, p = 2.0 × 10^-12). Mendelian randomization analyses demonstrate that …