Histology agnosticism: Infra-molecularizing disease?

The term "molecularization" has been used by historians and sociologists of science to describe the transition from an anatomic view of the body to a submicroscopic one, where health and illness, indeed life itself, are increasingly defined in terms of an individual's "genetic landscape." Here we introduce the notion of the infra-molecular as a way of extending and nuancing the molecularization trope as it applies to the domain of (post)genomic oncology. In particular we look at how infra-molecularity is enacted in practice as part of the so-called "histology-agnostic" turn in clinical cancer research and care. Drawing on fieldwork in North American oncology settings, we analyze how histology agnosticism partially reconfigures knowledge and practice across the linked domains of drug development and clinical trials, therapeutic decision making, and regulation, and the implications of this for an ongoing revision of how we understand the biopathology and temporality of cancer. We show how, in practice, the inframolecular gaze entails a "return" of histology as a modulator of histology-agnostic drugs and background for interpretation of mutational complexity.

Decision-making as discovery: Vetting clinical research in a leading precision oncology service.

Based on fieldwork carried out at the Early Drug Development Service of a world-leading cancer institution, our study sheds lights on decision-making processes at the stage where decisions are made about which clinical trial to pursue and thus which experimental drugs will feed the growing pipeline of molecularly guided therapies and therapeutic strategies available to treating physicians. The paper shows how such collective decision-making practices by a translational research unit employ formal tools and ad hoc valuation strategies that interweave technical-scientific matters of concern with patient-oriented clinical ones, as part of the institutional assetization of biomedical knowledge production. In the process, decision-making practices in part define the conditions of possibility for the provision of care in what is increasingly becoming a 'clinic of variants.' They do so by reconfiguring on an evolving basis the socio-material ecosystem through which precision oncology is enacted as a rapidly evolving assemblage of patients, physicians, research and support staff, protocols, molecular markers, drugs and administrative components.

Organizing precision medicine: A case study of Memorial Sloan Kettering Cancer Center's engagement in/with genomics.

Recent decades have seen a dramatic rise of in the number of initiatives designed to promote precision oncology, a domain that has played a pioneering role in the implementation of post-genomic approaches and technologies such as innovative clinical trial designs and molecular profiling. In this paper, based on fieldwork carried out at the Memorial Sloan-Kettering Cancer Center from 2019 onwards, we analyze how a world-leading cancer center has adapted, responded, and contributed to the challenge of "doing" precision oncology by developing new programs and services, and building an infrastructure that has created the conditions for genomic practices. We do so by attending to the "organizing" side of precision oncology and to the nexus between these activities and epistemic issues. We situate the work that goes into making results actionable and accessing targeted drugs within the larger process of creating a precision medicine ecosystem that includes purpose-built institutional settings, thus simultaneously experimenting with bioclinical matters and, reflexively, with organizing practices. The constitution and articulation of innovative sociotechnical arrangements at MSK provides a unique case study of the production of a large and complex clinical research ecosystem designed to implement rapidly evolving therapeutic strategies embedded in a renewed and dynamic understanding of cancer biology.

Multi-polar scripts: Techno-regulatory environments and the rise of precision oncology diagnostic tests.

The paper examines the development and marketing of five multi-gene tests, a.k.a. as tumor signatures, designed to aid clinicians and cancer patients in therapeutic decision-making, and, in particular, to avoid overtreatment. We build on a 2011 paper that investigated the emergence of this new domain by opening the 'black box' of two pioneering tests and analyzing the hybrid, scientific-regulatory 'scripts' that were built into them. In subsequent years, second-generation tests, produced by a diverse blend of academic and commercial initiatives, have become available, and they all built into their scripts the lessons learned from their predecessors. The present paper confirms the heuristic value of the initial script-analysis but expands it to consider the multi-polar nature of the space within which multigene tests mutually position themselves. We examine how the tests were first problematized - i.e. how they described and prescribed the kind of world in which they would operate - and how their initial problematization was re-specified following the emergence of a comparative arena and their resulting informational enrichment. In parallel, we explore valuation processes, i.e. the evolving definition of the set of referents against which the assays are mutually compared, and the debates about the appropriate criteria for doing so. We note that the cancer diagnostic industry is involved in the reconfiguration of the multi-polar environment defined by socio-technical, techno-scientific, and regulatory matters of concern that seamlessly blend commercial and scientific considerations.

Healthcare policy by other means: Cancer clinical research as "oncopolicy".

Social studies of biomedicine often focus on how exogenous policies shape the medical domain. While policy agendas no doubt affect complex biomedical projects, in the present paper we analyze a different dynamic, namely how oncologists enact policy as part of several flagship precision oncology endeavors. Empirically, the article focuses on the U.S. TAPUR trial, the Dutch DRUP trial, and the Canadian CAPTUR trial, which have recently been joined by similar Scandinavian studies. Taken together, these trials represent innovative forms of clinical research that, beyond their varying experimental nature, have been designed to transform the evidential processes to provide access to biomarker-driven treatments. Along with gathering evidence on effectiveness of off-label targeted therapies, their explicit goals include the recentering of a major professional organization around research, and the reframing of healthcare as a learning system seamlessly connecting epistemic, organizational, and economic issues. Accordingly, we analyze the design and implementation of these trials as a form of (onco)policy by other means.