Abstract
The promise of precision and personalized medicine is rooted in accurate, highly sensitive, and specific disease biomarkers. This is particularly true for cancer-a disease characterized by marked tumor heterogeneity and diverse molecular signatures. Although thousands of biomarkers have been described, only a very small number have been successfully translated into clinical use. Undoubtedly, there is need for rapid, quantitative, and more cost effective biomarkers for tumor diagnosis and prognosis, to allow for better risk stratification and aid clinicians in making personalized treatment decisions. This is particularly true for cancers where specific biomarkers are either not available (e.g., renal cell carcinoma) or where current biomarkers tend to classify individuals into broad risk categories unable to accurately assess individual tumor aggressiveness and adverse pathology potential (e.g., prostate cancer), thereby leading to problems of over-diagnosis and over-treatment of indolent cancer and under-treatment of aggressive cancer. This perspective highlights an emerging class of cancer biomarkers-live-single-cell phenotypic biomarkers, as compared to genomic biomarkers, and their potential application for cancer diagnosis, risk-stratification, and prognosis.
Highlights
Successful and meaningful biomarkers can be applied to different touch points in the diagnosis and treatment of disease
Live cell biomarkers are poised to be a powerful addition to available biomarkers and can be assessed either via slice cultures,[1] organoid cultures,[2] or single cell cultures.[3]
In the following we discuss the application of live-single-cell phenotypic biomarkers across the continuum of patient diagnosis and treatment
Summary
Successful and meaningful biomarkers can be applied to different touch points in the diagnosis and treatment of disease. Live cell biomarkers are poised to be a powerful addition to available biomarkers and can be assessed either via slice cultures,[1] organoid cultures,[2] or single cell cultures.[3] In the following we discuss the application of live-single-cell phenotypic biomarkers across the continuum of patient diagnosis and treatment. Cancer biomarkers have been broadly classified as either genomic (DNA/RNA) or phenotypic (morphology and protein expression). Analyses of live single-cell behavior suggest that dynamic biophysical cellular properties characterize both normal and disease states and represent a powerful extension and expansion of the concept of phenotypic biomarkers.[6] a working definition of phenotypic biomarkers may be expanded to consider spatial and temporal considerations, including two phenotypic biomarker sub-categories: molecular and cellular (Fig. 1a) either measured via live-cell microscopy or fixed-cell microscopy. Cellular phenotypic biomarkers include morphology, as well as live-cell biophysical parameters such as cell motility, contractility, force generation, and cytoskeletal dynamics. We summarize select cellular and molecular phenotypic biomarkers that have the potential to be translated and adopted into personalized novel quantitative and actionable cancer diagnostics and prognostics
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