Tracking extracellular vesicle phenotypic changes enables treatment monitoring in melanoma

Abstract

Monitoring targeted therapy in real time for cancer patients could provide vital information about the development of drug resistance and improve therapeutic outcomes. Extracellular vesicles (EVs) have recently emerged as a promising cancer biomarker, and EV phenotyping shows high potential for monitoring treatment responses. Here, we demonstrate the feasibility of monitoring patient treatment responses based on the plasma EV phenotypic evolution using a multiplex EV phenotype analyzer chip (EPAC). EPAC incorporates the nanomixing-enhanced microchip and the multiplex surface-enhanced Raman scattering (SERS) nanotag system for direct EV phenotyping without EV enrichment. In a preclinical model, we observe the EV phenotypic heterogeneity and different phenotypic responses to the treatment. Furthermore, we successfully detect cancer-specific EV phenotypes from melanoma patient plasma. We longitudinally monitor the EV phenotypic evolution of eight melanoma patients receiving targeted therapy and find specific EV profiles involved in the development of drug resistance, reflecting the potential of EV phenotyping for monitoring treatment responses.

The ins and outs of microvesicles

“…Researchers utilized microfluidic devices to examine phenotypic changes in melanoma extracellular vesicles to monitor treatment response, or to quantify the proteolytic activity of MT1-MMP for monitoring of in vivo tumor progression and metastasis. 79,80 As such, it is tempting to speculate on the future of EV clinical applications in exploiting the biochemical, physical, and functional makeup of EVs to improve diagnostics and real-time monitoring of disease.…”

Circulating extracellular vesicles are effective biomarkers for predicting response to cancer therapy

“…Moreover, Tucci et al found that higher expression of PD-1 and CD28 existed in immune cell-secreted EVs and may predict a good response to immunotherapy in metastatic melanoma [69], providing a new source of EVs. Wang et al studied the role of several specific proteins associated with melanoma therapy and progression in EVs, including melanoma chondroitin sulphate proteoglycan (MCSP), melanoma cell adhesion molecule (MCAM), low-affinity nerve growth factor receptor (LNGFR), and receptor tyrosine-protein kinase (ErbB3) [70]. The results indicated that these particular EVs were changing in different melanoma patients during and after targeted therapy [70].…”

Nanotechnology in emerging liquid biopsy applications

“…The detection and quantification of these biomarkers form a challenge due to their low amount in body fluids, the possibility of ctDNA fragmentation and instability of miRNA and RNA molecules. DNA sequencing is one of the most frequently used techniques in liquid biopsy applications; however, there is still a need for developing lower-cost and faster methods or devices that will provide increased portability, practicality, sensitivity and specificity, as well as the potential of multiplex analysis and point-of-care testing [ 21 , 22 ]. Nanomaterials have been exploited in liquid biopsy applications for signal improvement, due to the extremely low amounts of cancer ‘signature’ molecules present in body fluid samples.…”