Advances in the discovery of exosome inhibitors in cancer

Abstract

Exosomes are small membrane vesicles released by most eukaryotic cells. They are considered to play an essential role in cell-to-cell communication, and It is also found that they serve as functional mediators in many severe diseases, including progression of various types of cancers. Inhibition of exosome release may slow the progression of some cancers; thus, exosome has been an attractive target for cancer treatment. Over the years, considerable efforts have been made to discover novel, highly potent and excellently selective exosome inhibitors. Most of these inhibitors are derived from synthetic compounds, some of which are currently existed drugs and found to have the potential to inhibit exosome release. In this review, we briefly discussed the development of exosome inhibitors that are currently discovered and provided guidance for the future development of inhibitors.

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

“…Different studies also support a direct anti-tumor effect of PPI independently of cancer histology [ 11 ]. PPI are also useful, together with CA inhibitors, in downregulating exosome production, which is known to be involved in the progression of different human malignancies [ 220 ]. Furthermore, another advantage of PPI is that they are prodrugs needing acidity for their full activation, thus lowering any side effects while being more effective in the acidified TME conditions of malignant tumors.…”

Towards An Integral Therapeutic Protocol for Breast Cancer based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

“…Different studies also support a direct anti-tumor effect of PPI independently from cancer histology [10]. PPI are also useful, together with CA inhibitors, in downregulating exosome production, known to be involved in the progression of different human malignancies [210]. Furthermore, Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 23 September 2020 doi:10.20944/preprints202009.0534.v1…”

Small Extracellular Vesicles: A Novel Avenue for Cancer Management

“…As sEVs could remove damage-associated molecular patterns (DAMPs) from source cells to maintain intracellular homeostasis, inhibiting sEVs secretion can increase DAMPs levels in the cytoplasm, triggering cancer cell apoptosis (214). Cannabidiol, ketotifen, and simvastatin can block sEV biogenesis and release from cancer cells and monocytes through various mechanisms, which amongst others are linked to mitochondrial dysfunction and calcium dysregulation, thereby reversing chemotherapy resistance and magnifying antitumor immune responses (216)(217)(218)(219). Interestingly, these inhibitors target different steps of sEV biogenesis and secretion; thus, combination therapies could synergistically inhibit sEV secretion.…”