A pipeline for malignancy and therapy agnostic assessment of cancer drug response using cell mass measurements

一种利用细胞质量测量对癌症药物反应进行恶性肿瘤和治疗无关评估的流程

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作者:Robert J Kimmerling # ,Mark M Stevens # ,Selim Olcum # ,Anthony Minnah # ,Madeleine Vacha # ,Rachel LaBella # ,Matthew Ferri ,Steven C Wasserman ,Juanita Fujii ,Zayna Shaheen ,Srividya Sundaresan ,Drew Ribadeneyra ,David S Jayabalan ,Sarita Agte ,Adolfo Aleman ,Joseph A Criscitiello ,Ruben Niesvizky ,Marlise R Luskin ,Samir Parekh ,Cara A Rosenbaum ,Anobel Tamrazi ,Clifford A Reid

Abstract

Functional precision medicine offers a promising complement to genomics-based cancer therapy guidance by testing drug efficacy directly on a patient's tumor cells. Here, we describe a workflow that utilizes single-cell mass measurements with inline brightfield imaging and machine-learning based image classification to broaden the clinical utility of such functional testing for cancer. Using these image-curated mass measurements, we characterize mass response signals for 60 different drugs with various mechanisms of action across twelve different cell types, demonstrating an improved ability to detect response for several slow acting drugs as compared with standard cell viability assays. Furthermore, we use this workflow to assess drug responses for various primary tumor specimen formats including blood, bone marrow, fine needle aspirates (FNA), and malignant fluids, all with reports generated within two days and with results consistent with patient clinical responses. The combination of high-resolution measurement, broad drug and malignancy applicability, and rapid return of results offered by this workflow suggests that it is well-suited to performing clinically relevant functional assessment of cancer drug response.

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