Biomedical Engineering Reference
In-Depth Information
needs only 10% of tumor cells to stain positively for HER2, while an updated
scoring systems defines it as a uniform staining of more than 30%.
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Often, proof of concept can be shown with in vitro studies and the drug
carrier properties can be adjusted and perfected to show good results in a
murine model. Unfortunately, success is not only dependent on the drug
carrier.
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1.3.2
Challenges Present in the Target
It may be possible that some fairly effective magic bullets have been made.
While some may have failed because the wrong target was selected by design, it
is also possible that failure occurred because of target mutation and resistance.
A good portion of the targeting is passive and relies on the EPR effect. While
EPR has a lot of evidence in animal models, it could be studied more
extensively in human models as it does not always have a reliable effect.
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Figure 1.3 illustrates how therapeutics do not accumulate exclusively to nor
distribute evenly throughout the tumor. Studies in human patients evaluating
effectiveness of targeted delivery with scintigraphy show the difficulties of
avoiding accumulation in normal tissues.
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The unreliable EPR effect in clinical tumors shows the disparity between
human and animal models. Animal models help cancer research but there must
be some improvements in the models used to see significant improvements in
Figure 1.3
Representation of how typical clinical results show lack of preferential
targeting. (A) Targeted therapies accumulate in other organs and the
total accumulated amount is greater than that found in the tumors. (B)
The accumulation in the tumor is limited to the vascularized periphery
and does not penetrate to the core of the tumor.
