The potential of tumor-derived exosomes for noninvasive cancer monitoring

Abstract

Tumor-derived exosomes (TEX) are emerging as a new type of cancer biomarker. TEX are membrane-bound, virus-size vesicles of endocytic origin present in all body fluids of cancer patients. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by tumor cells and cancer cell-specific molecular and genetic contents, TEX are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of tumor cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma of cancer patients responding to therapies appear to correlate with clinical endpoints. However, methods for TEX isolation and separation from the bulk of human plasma-derived exosomes are not yet established and their role as biomarkers remains to be confirmed. Further development and validation of TEX as noninvasive, liquid equivalents of tumor biopsies are necessary to move this effort forward.

Keywords:

• cancer
• cancer prognosis
• molecular profiling
• non-invasive biomarkers
• nucleic acid content
• protein cargo
• tumor-derived exosome
• tumor-derived exosome isolation

Financial & competing interests disclosure

The author was in part supported by the NIH grant R0-1 CA16862. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Exosomes are the smallest type (30–120 nm) of extracellular vesicles present in human body fluids.

• Tumor-derived exosomes (TEX), a subset of exosomes, are avidly produced by tumor cells and accumulate in cancer patients’ plasma.

• Preclinical studies suggest that TEX mediate intercellular communication and are involved in a wide spectrum of other biological activities.

• TEX carry a cargo of proteins, lipids, glycans and nucleic acids, including mRNA, miRNA and DNA, which may be tumor-specific.

• Molecular and genetic components of TEX are biologically active in vitro and in vivo in murine cancer models.

• TEX have a potential of serving as a ‘liquid biopsy,’ which can be non-invasively monitored in the patient’s plasma.

• So far, TEX analysis has not been clinically applied to evaluate prognosis or responses to therapy in cancer.

• The lack of consensus on exosome and TEX isolation methods has been a major barrier in TEX development as cancer biomarkers.

• In the near future, intense efforts will be made to establish the role of TEX as surrogate markers of tumor progression, outcome and response to therapy.

Notes