Exosomes and Cancer

Cancer diagnosis and therapy is steadily improving. Still, diagnosis is frequently late and diagnosis and follow-up procedures mostly are time-consuming and expensive. Searching for tumor-derived exosomes (TEX) in body fluids may provide an alternative, minimally invasive, yet highly reliable diagnostic tool. Beyond this, there is strong evidence that TEX could become a potent therapeutics.Exosomes, small vesicles delivered by many cells of the organism, are found in all body fluids.

Exosomes are characterized by lipid composition, common and donor cell specific proteins, mRNA, small non-coding RNA including miRNA and DNA. Particularly the protein and miRNA markers received much attention as they may allow for highly specific diagnosis and can provide hints toward tumor aggressiveness and progression, where exosome-based diagnosis and follow-up is greatly facilitated by the recovery of exosomes in body fluids, particularly the peripheral blood. Beyond this, exosomes are the most important intercellular communicators that modulate, instruct, and reprogram their surrounding as well as distant organs. In concern about TEX this includes message transfer from tumor cells toward the tumor stroma, the premetastatic niche, the hematopoietic system and, last but not least, the instruction of non-cancer stem cells by cancer-initiating cells (CIC). Taking this into account, it becomes obvious that “tailored” exosomes offer themselves as potent therapeutic delivery system.

exosome rna

Therapeutic interference with TEX. Two therapeutic strategies are discussed, elimination of blocking of TEX and interfering with artificial/tailored exosomes . Elimination of TEX can be approached by plasmapheresis, blocking by interfering with exosome generation by destruction of the lipid bilayer, the ESCRT machinery, Rabs (e.g. by shRNA), antibody blocking at the target cell or the exosome level or by competition with non-TEX exosomes that are equipped with the TEX target structures. Active therapeutic interference relies on the transfer of cytotoxic drugs, like curcumin, an excess of oncomiR or metastomiR suppressing miRNA or blocking of oncomiR/metastomiR by various forms of anti-miR. Therapeutic delivery can be facilitated by special targeting advices and/or penetrating peptides.

In brief, during the last 4-5 years there is an ever-increasing, overwhelming interest in exosome research. This boom appears fully justified provided the content of the exosomes becomes most thoroughly analyzed and their mode of intercellular interaction can be unraveled in detail as this knowledge will open new doors toward cancer diagnosis and therapy including immunotherapy and CIC reprogramming.

Zöller M. (2016) Exosomes in Cancer Disease. Methods Mol Biol 1381:111-49. [abstract]

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