Tumors in animal models, mostly mice, are usually very “young” and immature. We inject cancerous cells in matrigell and start administering nanoparticles within the next few days or a week. In the case of human, cancer grows sometimes for many years, so cancer vascular system is much more developed and matured. Can we then compare passive (EPR) targeting in mice and humans? Are there any indisputable published data which proves EPR (based on nano size only) effect in humans?
The EPR is much more prominent in xenograft models in mice compared to actual tumors in humans. This is mostly due to the reasons you've mentioned. But it is known that the EPR effect is also common in some human cancers like the Kaposi's sarcoma and a few others. Some researchers also suggest to use dog models instead of mice models as there is a much better comparability to human cancer. If you want to read something about it, go check out the following review from Twan Lammers about pitfalls of drug targeting (includes EPR effect).
http://www.sciencedirect.com/science/article/pii/S0168365911008480
Agree with Robert, in addition the mouse models of cancer vary from one to another .For example the melanoma tumour vessels allow for particles in diameter of 400nm to pass through, on the other hand tumours like colon is quiet hard for particles more than 100nm to pass. so the type of xenograft model is important before even jumping to the human trails.
The EPR effect comes from the fact that growing cancer demands oxygen and nutrients, and produce chemical signals about its demands. This cause new vasculature to grow. This immature growing vasculature has leaky walls, what is a source of long residence time of nanoparticles in this area. Additionally lymphatic drainage is usually less developed then blood vascular system. So the EPR effect should be generally proportional to the grow rate of the cancer. Is that true?
Human cancer in its last stage also grows fast.
The EPR effect is extremely heterogeneous in humans and it works in rodents but not in humans! We cannot expect to find a “one size fits all” answer. It seems to me fighting against cancer should be as a multidisciplinary approach, first having data from personalized medicine (P7), individually, for of each patient , then using nano targeting therapy techniques ( passive or active) accompanied by enhancing the own body immune system within the treatment i.e.a combination treatment might be more effective.
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