Biography as Biology in Drug Development: Bio-Biographical Response States for Translational Pharmacology

IF 3.7 Q1 CHEMISTRY, MEDICINAL

ACS Pharmacology and Translational Science Pub Date : 2026-10-09 Epub Date: 2026-09-10 DOI:10.1021/acsptsci.6c00432

James B. Baker, Arnab Ghatak, Mark R. Cullen, Ralph I. Horwitz

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引用次数: 0

Abstract

Molecular stratification has improved drug development, yet treatment effects remain heterogeneous within apparently similar patients. We propose that selected lived exposures be studied as bio-biographical response states: prospectively measured combinations of experience, candidate mediator biology, and treatment context that may modify efficacy, toxicity, adherence, or end point ascertainment. This Perspective translates the concept into a falsifiable development framework. It defines pathway-specific hypotheses, consolidates trial-feasible measures, uses immuno-oncology as an implementation test case, and specifies stage-appropriate evidentiary gates. The framework does not treat adversity as destiny or assume that association establishes causation. It requires reliable measurement, formal interaction estimates, competing-explanation analyses, independent replication, and a defined decision consequence. Used with these guardrails, biography can complement molecular pharmacology by revealing reproducible host states that otherwise appear as unexplained response heterogeneity.

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生物学在药物开发中的作用：转化药理学的生物反应状态

分子分层改善了药物开发，但在明显相似的患者中治疗效果仍然不同。我们建议将选择的生活暴露作为生物生物学反应状态进行研究：前瞻性地测量经验、候选介质生物学和可能改变疗效、毒性、依从性或终点确定的治疗环境的组合。此透视图将概念转换为可证伪的开发框架。它定义了特定途径的假设，整合了试验可行的措施，使用免疫肿瘤学作为实施测试案例，并指定了适合阶段的证据门。该框架不把逆境视为命运，也不假设关联建立因果关系。它需要可靠的测量、正式的相互作用估计、竞争解释分析、独立的复制和定义的决策结果。与这些护栏一起使用，传记可以通过揭示可复制的宿主状态来补充分子药理学，否则会出现无法解释的反应异质性。

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

期刊介绍： ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.