Plasma signals of lung tumor promotion for molecular cancer prevention
Year: 2026
Type: article
Abstract: Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor ( EGFR )-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8 + /claudin4 + alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR , or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.
Source: Cell
Authors: Tej Pandya, Maria Zagorulya, Michelle M. Leung, Marcellus Augustine, Lydia Y. Liu, Aino-Maija Leppä, Ulysse Baruchel, Sin Wi Ng, Tamara Klockner, Miriam Mugabo, Anthony J. Griffen, Oleg Blyuss, Chrysante S. Iliakis, Amalie Grenov, Kerstin Haase, David C. Muller, Ka Hung Chan, Jincheng Wu, Vernon A. Burk, Neil Wright, Alix Le Marois, Ekaterina Pazukhina, Sophia Ward, Hubert Slawinski, Marc Pelletier, Cian Murphy, Matthew D. Park, Thomas Snoeks, Alejandro Suarez-Bonnet, Simon L. Priestnall, Alexandros Chardas, Charlotte Grieco, Ami Archer, Alpkaan Celik, Alejandro Jimenez-Sanchez, Rachel Scott, Hana Zahed, Léa Montégut, Rafael Meza, Clinton H. Durney, Stephen Lam, Takahiro Karasaki, Roel C.H. Vermeulen, Huilei Xu, Pablo Serrano-Fernandez, Tatjana Crnogorac-Jurcevic, Usha Menon, Sophia Apostolidou, Alexey Zaikin, Richard Gunu, Harry J. Whitwell, Zhe Huang, Zonglun Li, Xin Hu, Bo Zhu, Liming Li, María-Dolores Chirlaque, Marcela Guevara, P. Martijn Kolijn, Aghiles Guenoun, Neeloffer Mookherjee, Mattias Johansson, Ziqiao Wang, Nilanjan Chatterjee, Chao-Hua Chiu, Zhengming Chen, Dana Pe’er, Erik Sahai, Saskia Freytag, Andreas Wack, Marc J. Gunter, Miriam Merad, Jianjun Zhang, Christopher Carlsten, Pan-Chyr Yang, Hsuan-Yu Chen, Elizabeth A. Platz, Lindsay M. LaFave, Karl Smith-Byrne, Mariam Jamal-Hanjani, Kevin Litchfield, Nuno R. Nene, Nicholas McGranahan, Eva Grönroos, William Hill, Clare E. Weeden, Charles Swanton
Institutions: The Francis Crick Institute, Cancer Research UK, University College London, Walter and Eliza Hall Institute of Medical Research, Albert Einstein College of Medicine, Montefiore Health System, Montefiore Einstein Comprehensive Cancer Center, Queen Mary University of London, Sechenov University, Imperial College London, University of Oxford, Johns Hopkins University, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Royal Veterinary College, Memorial Sloan Kettering Cancer Center, Centre international de recherche sur le cancer, The University of Tokyo, Utrecht University, Novartis (Switzerland), Barts Cancer Institute, National Research University Higher School of Economics, The University of Texas MD Anderson Cancer Center, Peking University, Instituto Murciano de Investigación Biosanitaria, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Universidad de Murcia, Instituto de Salud Pública de Navarra, Navarre Institute of Health Research, University of Manitoba, Taipei Medical University Hospital, Taipei Medical University, Howard Hughes Medical Institute, The University of Melbourne, University of British Columbia, Vancouver Coastal Health Research Institute, National Taiwan University, Institute of Biomedical Sciences, Academia Sinica, Institute of Statistical Science, Academia Sinica, University of Manchester, Cancer Research UK Manchester Institute
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $11,400
Funders: U.S. Department of Health and Human Services, American Association for Cancer Research, Breast Cancer Research Foundation, Damon Runyon Cancer Research Foundation, V Foundation for Cancer Research, European Molecular Biology Organization, Cancer Prevention and Research Institute of Texas, Lung Cancer Research Foundation, Compagnia di San Paolo, European Respiratory Society, Centre International de Recherche sur le Cancer, Wellcome Trust, Francis Crick Institute, Skin Treatment and Research Trust, A Breath of Hope Lung Foundation, Hope Foundation, UK Research and Innovation, Mark Foundation For Cancer Research, Barts Charity, State of Maryland, Cancer Research UK, National Institute for Health and Care Research, Royal Society, Japan Society for the Promotion of Science London, University College London, Rosetrees Trust, ZonMw, Ministerie van Volksgezondheid, Welzijn en Sport, Ministero della Salute, Associazione Italiana per la Ricerca sul Cancro, Junta de Andalucía, Novo Nordisk Foundation Center for Basic Metabolic Research, CRUK Lung Cancer Centre of Excellence, Ministero dell'Università e della Ricerca, National Institutes of Health, Centers for Disease Control and Prevention, Imperial Experimental Cancer Medicine Centre, Canadian Institutes of Health Research, Medical Research Council, Engineering and Physical Sciences Research Council, World Cancer Research Fund, European Research Council, Japan Society for the Promotion of Science, Instituto de Salud Carlos III, UCLH Biomedical Research Centre, School of Public Health, Imperial College London, National Heart, Lung, and Blood Institute, National Cancer Institute, H2020 Marie Skłodowska-Curie Actions, Human Developmental Biology Resource, Stoneygate Trust
Awards: Aetiology of type 2 diabetes and related metabolic disorders, G1188886465, G1595129242, G1829357131, G2103396735, G2287024733, G2628619148, MARYLAND CANCER PREVENTION AND CONTROL PROGRAM - THE GOAL OF THE MARYLAND CANCER PREVENTION AND CONTROL PROGRAM IS TO IMPLEMENT CANCER PREVENTION AND CONTROL PROGRAMS TO REDUCE MORBIDITY, MORTALITY, AND RELATED HEALTH DISPARITIES IN MARYLAND. PROGRAM 1: NATIONAL BREAST AND CERVICAL CANCER EARLY DETECTION PROGRAM THE MARYLAND BREAST AND CERVICAL CANCER EARLY DETECTION PROGRAM (MBCCEDP) WILL IMPLEMENT A COMPREHENSIVE, DATA-DRIVEN, AND HEALTH EQUITY-FOCUSED APPROACH TO DECREASE BREAST AND CERVICAL CANCER DISPARITIES, MORBIDITY, AND MORTALITY IN THE STATE OF MARYLAND. MBCCEDP OVERSEES 16 DIRECT SCREENING PROGRAMS ACROSS THE STATE THAT PROVIDE VULNERABLE WOMEN WITH QUALITY BREAST AND CERVICAL CANCER SCREENING, DIAGNOSTIC, AND PATIENT NAVIGATION SERVICES. MBCCEDP WORKS WITH STATE, REGIONAL, AND LOCAL PARTNERS TO INCREASE CLIENT RECRUITMENT EFFORTS AND LINK WOMEN TO APPROPRIATE RESOURCES SUCH AS A MEDICAL HOME AND HEALTH INSURANCE MARKETPLACES. ADDITIONALLY, MBCCEDP PARTNERS WITH HEALTH SYSTEMS AND PRIMARY CARE CLINICS TO INCORPORATE SUSTAINABLE EVIDENCE-BASED INTERVENTIONS INTO THEIR STANDARD OF CARE. MBCCEDP WILL WORK TOWARDS THE GOAL OF ELIMINATING DISPARITIES IN BREAST AND CERVICAL CANCER SCREENING AND OUTCOMES. MBCCEDP SERVES LOW-INCOME, UNINSURED AND UNDERINSURED WOMEN IN MARYLAND. HOWEVER, AS BLACK AND AFRICAN AMERICAN WOMEN IN MARYLAND EXPERIENCE SIGNIFICANTLY HIGHER LATE-STAGE DIAGNOSES AND HIGHER MORTALITY RATES COMPARED TO OTHER GROUPS, MBCCEDP WILL ALLOCATE RESOURCES, ENGAGE PARTNERS, AND MONITOR OUTCOMES TO PRIORITIZE THE BLACK AND AFRICAN AMERICAN POPULATION UNDER THIS COOPERATIVE AGREEMENT. THE HISPANIC POPULATION, WHICH MAKES UP A LARGE PERCENTAGE OF UNINSURED MARYLANDERS AND FACES ENGLISH-PROFICIENCY AND OTHER BARRIERS TO HEALTH CARE ACCESS, WILL BE A SECOND TARGET POPULATION FOR MBCCEDP. PROGRAM 2: NATIONAL COMPREHENSIVE CANCER CONTROL PROGRAM THE GOAL OF THE MARYLAND COMPREHENSIVE CANCER CONTROL PROGRAM (MCCCP) IS TO ADDRESS CANCER PREVENTION AND CONTROL ISSUES IN THE STATE OF MARYLAND BY CONVENING STAKEHOLDERS, USING AND SHARING SURVEILLANCE AND OTHER DATA, AND IMPLEMENTING FORMAL PLANS TO REDUCE THE BURDEN OF CANCER IN THE STATE. MCCCP FOCUSES ON IMPLEMENTING EVIDENCE-BASED INTERVENTIONS TO INCREASE AND IMPROVE PRIMARY PREVENTION, EARLY DETECTION AND SCREENING, AND THE HEALTH AND WELLBEING OF CANCER SURVIVORS. MCCCP ESTABLISHED THE MARYLAND CANCER COLLABORATIVE (MCC) IN 2011, BRINGING TOGETHER DIVERSE STAKEHOLDERS TO DEVELOP AND IMPLEMENT THE MARYLAND COMPREHENSIVE CANCER CONTROL PLAN, WHICH GUIDES CANCER PREVENTION AND CONTROL PRIORITIES IN THE STATE OF MARYLAND. MCCCP WILL MAINTAIN, SUPPORT, AND ENGAGE THE MCC AND MCC WORKGROUPS THROUGHOUT THE FIVE-YEAR PROJECT PERIOD. MCCCP WILL ALSO ESTABLISH, MAINTAIN, AND/OR SUPPORT OTHER ACTIVE STAKEHOLDER GROUPS IN MARYLAND, INCLUDING THE PATIENT NAVIGATION NETWORK, HUMAN PAPILLOMAVIRUS (HPV) TASK FORCE, MARYLAND COLORECTAL CANCER TASK FORCE, AND LUNG CANCER COLLABORATIVE. INTERNALLY, MCCCP WILL CONTINUE TO FOSTER REGULAR COLLABORATION AMONG OTHER CENTERS FOR DISEASE CONTROL AND PREVENTION- AND STATE-FUNDED CANCER AND CHRONIC DISEASE PROGRAMS, SHARING THE MCCCP’S EXPERTISE IN IMPLEMENTING POLICY, SYSTEMS, AND ENVIRONMENTAL APPROACHES AND CLINICAL-COMMUNITY LINKAGES. PROGRAM 3: NATIONAL PROGRAM OF CANCER REGISTRIES THE MARYLAND CANCER REGISTRY (MCR) AIMS TO REDUCE THE BURDEN OF CANCER IN MARYLAND. UNDER THIS COOPERATIVE AGREEMENT, THE MCR WILL WORK TOWARD THIS GOAL BY CONTINUING TO COLLECT DATA ON ALL THE INCIDENCE CASES OF CANCER IN THE STATE OF MARYLAND. THE COLLECTED DATA WILL BE USED TO MONITOR TRENDS AND PATTERNS IN CANCER INCIDENCE, GUIDE THE PLANNING AND EVALUATION OF CANCER CONTROL PROGRAMS, HELP SET PRIORITIES FOR ALLOCATING PUBLIC HEALTH AND HEALTH CARE RESOURCES, ASSESS CANCER CLUSTER CONCERNS, PROVIDE INFORMATION FOR A NATIONAL DATABASE OF CANCER INCIDENCE, AND EXCHANGE CANCER DATA WITH OTHER STATES TO ASSURE MORE COMPLETE AND ACCURATE INCIDENCE DATA., G3038870994, G3189771268, G3194548215, G3291420878, G3328679326, G3795408166, G3931319179, G3978702139, G4179415125, G419357997, G4275441869, G4397751285, The EPIC-Norfolk prospective population study: biological and behavioural determinants of health and disease in an ageing population, G5058239881, Long term impact of screening on ovarian cancer mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), G5095926048, G518414402, G527520901, G5315906942, G5641902599, Profiling Cardiovascular Events and Biomarkers in the Very Old to Improve Personalized Approaches for the Prevention of Cardiac and Vascular Disease, G5724888378, G5769131704, G5874233344, Precision Lung Cancer Interception by Targeting High-Risk Lung Nodules, G6522009272, G6821251212, G6915178885, G7269663634, EPIC-Oxford: benefits and risks of plant-based diets, G7700411375, G7894469207, G8410755691, G8666488740, Evaluating new healthcare technologies in cancer, G924720359
OpenAlex ID: W7163591960