دانلود رایگان مقاله انگلیسی حامل های خارج سلولی و مقاومت به داروهای ضد سرطان - الزویر 2018

ABSTRACT

Extracellular vesicles (EVs) including exosomes, microvesicles, oncosomes, and microparticles have been associated with communicating anti-cancer drug-resistance. The in vitro, pre-clinical in vivo and patients' data linking EVs to drug-resistance (and the specific drugs involved) in breast cancer, prostate cancer, lung cancer, ovarian cancer, haematological malignancies, colorectal cancer, gastric cancer, pancreatic cancer, glioblastoma, neuroblastoma, melanoma, kidney cancer and osteosarcoma. Details of the mechanisms by which the resistance seems to be occurring (e.g. EVs transferring drug-efflux pumps from drug-resistant cancer cells, EVs binding monoclonal antibodies in the peripheral circulation and so reducing their bioavailability, EVs from tumour microenvironment cells, etc.) are outlined, as are efforts to try to block such resistance. Research to date strongly supports EVs as playing a key role in drug-resistance. Further studies including tailored clinical studies are now warranted to determine how best to prevent this occurring, in the interest of patients and also for economic benefit. Furthermore, efforts to exploit safe (non-cancer origin) EVs as anti-cancer drug delivery vehicles that may achieve efficacy with more limited side-effects than free drug, deserve further investigation.

Conclusion

It is evident from multiple studies by multiple research groups across both solid and non-solid cancer types that EVs from drug-resistant cancer cells and/or tumour microenvironment cells (Fig. 3) are causally involved in transmitting resistant to anti-cancer drugs thus contributing to challenges experienced with anti-cancer treatments. Through in vitro, pre-clinical in vivo and/or ex vivo studies on patients' specimens it is evident that the EVs involvement is via numerous mechanisms. We propose that larger multi-institutional studies including more pre-clinical and clinical analyses, using consistent and best methods for EV isolation and evaluation, and samples sharing for independent validation are now warranted to move this field forward, in a timely way, for the benefit of patients. Furthermore, while still in its infancy as a research area, studies to date investigating the utility of EVs as naturally delivery vehicles for anti-cancer molecules -in order to achieve efficacy at lower drug doses and so with reduced side-effectssuggest that this approach holds much promise.