Research Lecture at Nobel Forum by Charles Swanton
Date: September 17th 2026, 1 pm
Cancer Promotion and Preventing Pathologies of Ageing
Professor Charles Swanton, Deputy Clinical Director at the Francis Crick Institute, London, UK; Chief Clinician at Cancer Research UK
Cancer is overwhelmingly a disease of ageing. Oncogenic mutations accumulate in expanding clones throughout normal tissue over a lifetime, so by mid-life much of our epithelium is a mosaic of mutant fields. If initiation is near-ubiquitous, why do so few clones progress? Emerging evidence suggests that a rate-limiting event is not initiation but promotion, and that the promoter is frequently inflammation, with myeloid programmes at its heart across the natural history of lung cancer.
At initiation, particulate-matter exposure drives alveolar macrophages to release IL-1β, priming mutant epithelial cells to expand through a keratin 8⁺/claudin 4⁺ alveolar transitional state. This biology is captured by a 14-protein plasma signature, derived from UK Biobank proteomics and validated across eight global cohorts, that predicts incident lung cancer >5 years in advance of diagnosis and, applied to CANTOS, identifies those who benefit from anti-IL-1β prevention. Because CANTOS was a cardiovascular trial, the same IL-1β axis links lung cancer and cardiovascular disease as shared pathologies of ageing. A similar myeloid axis governs the later trajectory of disease. Age-related clonal haematopoiesis, particularly involving TET2-mutant clones, seeds tumours with mutant monocytes that accumulate as CD11b⁺ macrophages, remodel the microenvironment, accelerate tumour organoid growth, and independently predict recurrence and death across TRACERx NSCLC patients and over 49,000 individuals in the MSK-IMPACT pan-cancer cohort. This phenomenon, termed tumour-infiltrating clonal haematopoiesis (TI-CH) connects the ageing haematopoietic system directly to cancer evolution and progression.
Together, these data linking environmental exposures with age-related somatic mosaicism offer a tractable framework for molecular prevention, targeting nodal inflammatory axes driving both lung cancer and cardiovascular pathologies of ageing.
Venue: Wallenbergsalen, Nobel Forum, Karolinska Institutet, Nobels väg 1
Host: Richard Rosenquist Brandell, MD, PhD, Professor of Clinical Genetics, Karolinska Institutet, richard.rosenquist@ki.se
Contact: Pernilla Witte, Nobel Office, nobelforum@nobelprizemedicine.org