My brothers molecular report states that he has mdm2 mutation or something like that and that nutlin3 would be usefull. Since nutlin 3 is not available I am looking for something else instead. Here is a study I found about verapamil acting similar to nutlin3. What do you think about it? http://www.nature.com/bjc/journal/v111/n4/fig_tab/bjc2014325f4.html
Unfortunately this study is not saying that verapamil is an MDM2 antagonist, like nutlin 3. It is saying that verapamil inhibits MDR-1 (also known as P-glycoprotein), which nutlin-3 does as well. So while verapamil may be useful as a P-glycoprotein inhibitor, it can't replace nutlin-3 as an MDM2 antagonist.
The significance of MDM2 amplification: MDM2 is a negative regulator of p53 (which is a tumor suppressor in its non-mutant form). So the more MDM2, the less p53.
Nutlin-3 is an experimental drug, still in early stage clinical trials for cancer. I have never heard of it being used in human brain tumor patients.
ReplyDeleteMy brothers molecular report states that he has mdm2 mutation or something like that and that nutlin3 would be usefull. Since nutlin 3 is not available I am looking for something else instead. Here is a study I found about verapamil acting similar to nutlin3.
ReplyDeleteWhat do you think about it?
http://www.nature.com/bjc/journal/v111/n4/fig_tab/bjc2014325f4.html
Unfortunately this study is not saying that verapamil is an MDM2 antagonist, like nutlin 3. It is saying that verapamil inhibits MDR-1 (also known as P-glycoprotein), which nutlin-3 does as well. So while verapamil may be useful as a P-glycoprotein inhibitor, it can't replace nutlin-3 as an MDM2 antagonist.
DeleteThe significance of MDM2 amplification: MDM2 is a negative regulator of p53 (which is a tumor suppressor in its non-mutant form). So the more MDM2, the less p53.
DeleteIt looks like telmisartan (an angiotensin II receptor blocker) might be a way to block the MDM2-p53 interaction, similar to nutlin-3.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/24554192
There has also been retrospective studies showing GBM patients taking this class of drug have improved survival.