{"entity":{"id":"idea-bio1-aged-comorbid-models","kind":"idea","name":"Test cancer drugs in old and unhealthy animals, not just young fit ones","aka":[],"tldr":"Most cancer patients are older and have other illnesses, but nearly all animal experiments use young healthy mice. Results may not transfer.","summary":"Ageing changes immune function, drug metabolism, marrow reserve and the tumour microenvironment; obesity and diabetes alter drug distribution and immunotherapy response. Efficacy and toxicity studies in aged, obese or comorbid animals cost more and take longer, so they are rarely done. Requiring at least one aged-cohort confirmation before first-in-human studies of immunotherapies would be a targeted change.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-aging-comorbidity"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For a meaningful minority of agents, efficacy or toxicity in aged or obese animals differs materially from young lean animals in a direction that predicts clinical experience in older patients.","rationale":"Age-related immune decline is documented in mice and humans, and obesity paradoxically improves some immunotherapy outcomes; these interactions are invisible in the standard young mouse.","test":"Repeat pivotal efficacy studies for ten agents with known clinical outcomes in aged and diet-induced obese cohorts and compare which model better matches the clinical result.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio1-aged-comorbid-models/","neighbours":{"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"term":[{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"}],"bottleneck":[{"id":"b-preclinical-models","kind":"bottleneck","name":"Lab models that fail to predict what happens in patients","route":"/bottlenecks/b-preclinical-models/"},{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/"}],"paper":[{"id":"paper-wong-biostatistics","kind":"paper","name":"Estimation of clinical trial success rates and related parameters","route":"/key-papers/paper-wong-biostatistics/"}]}}