Precision oncology, defined as the use of the molecular understanding of cancer to implement personalized patient treatment, is currently at the heart of revolutionizing oncology practice. Due to the need for repeated molecular tumor analyses in facilitating precision oncology, liquid biopsies, which involve the detection of noninvasive cancer biomarkers in circulation, may be a critical key. Yet, existing liquid biopsy analysis technologies are still undergoing an evolution to address the challenges of analyzing trace quantities of circulating tumor biomarkers reliably and cost effectively. Consequently, the recent emergence of cutting‐edge plasmonic nanomaterials represents a paradigm shift in harnessing the unique merits of surface‐enhanced Raman scattering (SERS) biosensing platforms for clinical liquid biopsy applications. Herein, an expansive review on the design/synthesis of a new generation of diverse plasmonic nanomaterials, and an updated evaluation of their demonstrated SERS‐based uses in liquid biopsies, such as circulating tumor cells, tumor‐derived extracellular vesicles, as well as circulating cancer proteins, and tumor nucleic acids is presented. Existing challenges impeding the clinical translation of plasmonic nanomaterials for SERS‐based liquid biopsy applications are also identified, and outlooks and insights into advancing this rapidly growing field for practical patient use are provided.

An extracellular vesicle phenotype analyzer chip shines a light on patients’ responses to targeted therapy in cancer.

Real-time monitoring of cancer cells’ phenotypic evolution during therapy can provide vital tumour biology information for treatment management. Circulating tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its routine usage is restricted by either limited multiplexing capability or sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as “cell signature”), without the need for isolating individual CTCs. We observe cell heterogeneity and phenotypic changes of melanoma cell lines during molecular targeted treatment. Furthermore, we follow the CTC signature changes of 10 stage-IV melanoma patients receiving immunological or molecular targeted therapies. Our technique maps the phenotypic evolution of patient CTCs sensitively and rapidly, and shows drug-resistant clones having different CTC signatures of potential clinical value. We believe our proposed method is of general interest in the CTC relevant research and translation fields.