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Biography \u2014 chronic stress, adversity, trauma, and social isolation\u2014is a neglected source of that heterogeneity, operating through the same molecular pathways drugs engage. Independent studies in non\u2010small cell lung cancer and melanoma have demonstrated that pretreatment biographical measurement predicts immune checkpoint inhibitor response through measurable immunological intermediaries, providing existence proof that this axis of heterogeneity is both detectable and pharmacologically consequential. Bio\u2010biographical mechanistic profiling (BBMP) is the prospective, mechanism\u2010matched measurement of biographical factors alongside standard biomarkers, designed to identify patients in whom biography has modified the pathway a drug is intended to engage. Matching treatment to pathway is not the same as matching treatment to a person in whom that pathway has been constituted by biography. BBMP is designed to close that gap.<\/jats:p>","DOI":"10.1002\/cpt.70429","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:04:13Z","timestamp":1786593853000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biography as the Missing Variable in Drug Development: A Case for Bio\u2010Biographical Mechanistic Profiling"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-2723","authenticated-orcid":false,"given":"Ralph I.","family":"Horwitz","sequence":"first","affiliation":[{"name":"Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1571"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315878"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.11061"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182115"},{"key":"e_1_2_9_5_1","first-page":"1591","article-title":"Inhibition of IL\u20106+IL\u20106 soluble receptor\u2010stimulated aromatase activity by the IL\u20106 antagonist, Sant 7, in breast tissue\u2010derived fibroblasts","volume":"86","author":"Knower K.C.","year":"2002","journal-title":"Br. 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