Thanks for the link Danny. The full study can be downloaded at Oncotarget: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=8720&pubmed-linkout=1
Unfortunately, but typically, the drugs were all tested at a high concentration (see figure 6A and 6B in the study) of 10 micromolar. The currently available drugs that showed effect at this concentration were rapamycin, all trans retinoic acid (ATRA) and metformin. The 10 micromolar concentration is close to physiological levels for metformin, but not for rapamcyin or ATRA (it is 500 to 10,000 times too high for rapamycin, and while you can get low micromolar values of ATRA in the plasma, the free fraction is less than 5%).
Metformin increased NFIB expression by 33%, but was not one of the four drugs shown to inhibit proliferation of a low passage GBM cell line at this concentration.
All 3 of these drugs certainly have use in cancer, but whether these drugs affect this particularly pathway at concentrations achievable in vivo would require further follow up studies.
Thanks Stephen. Just adds another factor of whether I should add Metformin to my long term lowgrade deleted idh1 mutated Oligo. On a side note: is there a larger umbrella you and others dedicated to the cocktail approach are collaborating under where we could donate funds to directly help the cause?
Thanks for the link Danny. The full study can be downloaded at Oncotarget:
ReplyDeletehttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=8720&pubmed-linkout=1
Unfortunately, but typically, the drugs were all tested at a high concentration (see figure 6A and 6B in the study) of 10 micromolar. The currently available drugs that showed effect at this concentration were rapamycin, all trans retinoic acid (ATRA) and metformin. The 10 micromolar concentration is close to physiological levels for metformin, but not for rapamcyin or ATRA (it is 500 to 10,000 times too high for rapamycin, and while you can get low micromolar values of ATRA in the plasma, the free fraction is less than 5%).
Metformin increased NFIB expression by 33%, but was not one of the four drugs shown to inhibit proliferation of a low passage GBM cell line at this concentration.
All 3 of these drugs certainly have use in cancer, but whether these drugs affect this particularly pathway at concentrations achievable in vivo would require further follow up studies.
Thanks Stephen. Just adds another factor of whether I should add Metformin to my long term lowgrade deleted idh1 mutated Oligo. On a side note: is there a larger umbrella you and others dedicated to the cocktail approach are collaborating under where we could donate funds to directly help the cause?
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