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mechanisms of these signals seem to be more complex than their than patients receiving chemotherapy alone.
Endostar has now been
proangiogenic counterparts. For example, Tsp-1 has been reported to approved for the treatment of lung cancer in China and trials are in
interact with several different receptors, although much of the angiostatic progress for the treatment of other cancer types.
activity is thought to be mediated through the CD36 receptor. The use of
Tsp-1 as a therapeutic is also complicated by the fact that it is a very large We have observed the p53 tumor suppressor to stimulate the release of
protein that would be difficult to produce in sufficient quantities for at least two different CDAFs, endostatin and tumstatin.
It is likely that
treatment. This is not the case for the CDAFs, which are relatively small using cocktails of CDAFs may prove more effective. CDAFs function by
16–20kDa peptides and can be adapted almost directly as drugs. binding to integrin molecules on endothelial cells, and each CDAF has
slightly different properties.
Since p53 can stimulate production of at
There is evidence that increasing production of CDAFs can have a least two different CDAFs, using such mixtures may be a more effective
significant effect on tumor growth. Studies in mice have shown that method of shutting down angiogenesis. Another strategy used by p53
increasing levels of endostatin by only 1.6-fold can result in lower tumor that may prove clinically relevant is to utilize therapies that target
In this same study it was also shown that mice lacking the proangiogenic signals such as VEGF in combination with CDAFs. Drugs
expression of the CDAFs endostatin or tumstatin result in two- to that target VEGF such as bevacizumab have been approved for treatment
three-fold faster tumor growth. Unfortunately, when phase II clinical of lung and colorectal cancer and are able to extend the life of patients
trials for endostatin were carried out for the treatment of advanced by four to six months. Unfortunately, tumors eventually develop
neuroendocrine tumors, no significant tumor regression was observed.
resistance to these medications and evolve other routes by which to
The lack of response in this study may have been due to the type and late promote angiogenesis. Preventing tumor vascularization may be
stage of the cancers under study, as well as the protocol of using analogous to fighting infectious diseases such as HIV. The control of
endostatin as a monotherapy. Since this initial report, no further trials angiogenesis in cancer may be achieved only through the application of
using CDAFs have been carried out at any sites in North America or well-designed cocktails of drugs targeting several aspects of
Europe. However, several clinical trials are being carried out in China angiogenesis biology. Tumor-suppressor proteins such as p53 are able to
using a modified version of endostatin called Endostar. Results of trials hold angiogenesis in check for extended periods of time, and studying
using chemotherapy in combination with Endostar for treatment of lung such pathways may provide insights toward how tumor angiogenesis can
cancer have been reported to show significantly greater tumor regression be controlled in the clinic. ■
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