"Angiogenesis Promoting Gene Patterns in Alveolar Soft Part Sarcoma" - this
new excellent study is done by MDA and published in the Clin.Cancer Research Dec.15, 2007 issue.
They analyzed tissue samples from the 33 patients (half of them were from primary tumors and half of them metastases) and found 18 unregulated angiogenesis-related genes and they were not the commonly up-regulated VEGF, fibroblast growth factors, platelet derived growth factor, angiopoietins or matrix metalloproteases. They were present too but not upregulated. The most upregulated genes were midkine, angiogenin, jag-1, HIF1a and TGF-beta. One of this factors - midkine - is associated with the neuronal cells and might be responsible for the high frequency of ASPS brain mets.
We will soon have the PDF of this article inserted in the Characterization of ASPS tumors part of the library on the front page, probably later on today.
There might be no much use in the targeted therapies that DO NOT target these specific genes, as although their corresponding targets might be expressed in ASPS but not upregulated and the effects will be most probably weak and short (it is my own unqualified opinion).
These factors are found upregulated in some other diseases and for example angiogenin has been found to have a dual effect, angiogenesis and cancer cell proliferation, in prostate cancer, so according to the study from the Center for Biochemical and Biophysical Sciences and Medicine, Department of Pathology, Harvard Medical School -
Blocking nuclear translocation of angiogenin could have a combined benefit of antiangiogenesis and chemotherapy in treating prostate cancer - it might be the same in ASPS?
ASPS angiogenic signature is unique
ASPS angiogenic signature is unique
Last edited by Olga on Mon Jan 07, 2008 6:05 am, edited 1 time in total.
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Fictional
This is an interesting finding, Olga. But I would caution families about necessarily writing off the use of existing anti-angiogenesis factors based on the findings in this study. The are technical reasons - RT PCR, formalin-fixed paraffin block tissue, that limit the study. The Slavc study took fresh tissue (from a brain metastasis) and did in situ hybridization that combined VEGF and VEGF Receptor mRNA. Also they saw a clinical (albeit partial) response to Avastin.
There is evidence that anti-angiogenesis factors are not enough - i.e. they may need to be combined with other treatments for complete response. And yet these factors may have value because they may limit growth, induce some cell death, and reduce the microvessel which not only supply more nutrients to the tumor cells, but also allow the tumor cells to escape and form more metastases elsewhere.
There is also some murmurings by researchers that continuous dosing (lower dose) may be more effective because it does not allow the tumor to regrow or rebound during the off cycle.
There is evidence that anti-angiogenesis factors are not enough - i.e. they may need to be combined with other treatments for complete response. And yet these factors may have value because they may limit growth, induce some cell death, and reduce the microvessel which not only supply more nutrients to the tumor cells, but also allow the tumor cells to escape and form more metastases elsewhere.
There is also some murmurings by researchers that continuous dosing (lower dose) may be more effective because it does not allow the tumor to regrow or rebound during the off cycle.