Hi Yiming, just to lay my cards on the table. I don't think exosomes in liquid biopsies are of any value whatsoever.
The circulation has ~10,000 Km of blood vessels and cells are constantly dying and being regenerated. Therefore, at any time the blood is full of exosomes.
How do you distinguish regular exosomes from cancer exosomes?
As far as I know you cant. It is like isolating DNA from plasma. What DNA is transformed and which is not?
Which DNA is derived from stromal cells supporting tumor growth and which are derived from tumor cells?
It is like looking for a needle in a haystack and you don't know what the needle looks like or what it is made of.
Thanks for answering my question. That maybe a new idea for me to swallow up, but in the same time,I thought there really exist some difficulties in exosome collection and identification. I'm so appreciated that you share your opinion with me and wishing you a great day!
according to the many papers and protocols and laboratory products released during the last few years the usefulness of circulating stuff may be just a matter of sensitivity and thresholds. I might also agree on the fact that isolating ctDNA from plasma is like looking for a needle in a hastack but if that needle can be actually used to detect EGFR mutations in non-small cell lung cancer (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887309/) or other cancers (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492590/) it may be wise not to underestimate the related potential.
Moreover the scenario is not so simple: we do not even need to isolate and characterize strictly tumor derived exosomes since exosome release from normal cell may be also affected by the disease producing associated perturbation on the global exosome signature. I'm really not so sure about the uselessness of EVs' applications in liquid biopsy, and I'm quite sure I'm not alone.