Post by Allen on Jul 29, 2014 21:48:45 GMT -8
Histone Deacetylase Inhibitors (HDACIs)
Here's a good explanation of what this class of drugs do and why they are important in cancer:
Histone Deacetylase Inhibitors: Overview and Perspectives
This class of drugs may cause PC cells to differentiate; i.e., lower Gleason grade. There may be other mechanisms as well for its effectiveness against prostate cancer.
There are three main subtypes: butyrates, hydroxamic acids, and valproates:
Sodium butyrate is a substance found in our guts as a product of fiber degradation. It seems to be safe even in multi-gram amounts, and is sold as a supplement on the internet. It seems to have its differentiating effect only on cancer cells.
Perhaps because it is so inexpensive and non-patentable, I haven’t seen any human clinical trials of it. There is a more potent analogue called tributyrin. There has been a Phase 1 clinical trial (NCT00002677), but I haven’t seen any reported results.
Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer
Vorinostat, an HDACi approved for use with cutaneous T-cell lymphoma, failed to show significant efficacy when tried as a monotherapy in men progressing after chemo.
Valproic Acid (Depakote) is a well-known anti-epileptic and mood stabilizer that was recently discovered to have powerful anti-cancer effects. It and other HDACIs are in clinical trials against prostate cancer.
Valproic Acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
There is a clinical trial (NCT00670046) at Johns Hopkins of its use in men with PC progressing after treatment.
In human trials, the combination of valproic acid and an angiogenesis inhibitor (see angiogenesis inhibitor thread) has been safe and effective in several advanced cancers including PC.
Phase I study of anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers.
There is evidence from lab and animal studies that it may be most effective when combined with mTOR inhibitors (see mTOR thread)
• Synergistic effects of histone deacetylase inhibitor in combination with mTOR inhibitor in the treatment of prostate carcinoma.
• Impact of combined HDAC and mTOR inhibition on adhesion, migration and invasion of prostate cancer cells.
• Inhibitory effects of the HDAC inhibitor valproic acid on prostate cancer growth are enhanced by simultaneous application of the mTOR inhibitor Everolimus
Safety
Valproic Acid has been used in the treatment of epilepsy for almost 30 years. It exhibits several additional biological activities, in particular beneficial effects in migraine as well as side effects such as teratogenicity and, rarely, liver toxicity. It has only mild adverse effects in adults.
Here's a good explanation of what this class of drugs do and why they are important in cancer:
Histone Deacetylase Inhibitors: Overview and Perspectives
This class of drugs may cause PC cells to differentiate; i.e., lower Gleason grade. There may be other mechanisms as well for its effectiveness against prostate cancer.
There are three main subtypes: butyrates, hydroxamic acids, and valproates:
Sodium butyrate is a substance found in our guts as a product of fiber degradation. It seems to be safe even in multi-gram amounts, and is sold as a supplement on the internet. It seems to have its differentiating effect only on cancer cells.
Perhaps because it is so inexpensive and non-patentable, I haven’t seen any human clinical trials of it. There is a more potent analogue called tributyrin. There has been a Phase 1 clinical trial (NCT00002677), but I haven’t seen any reported results.
Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer
Vorinostat, an HDACi approved for use with cutaneous T-cell lymphoma, failed to show significant efficacy when tried as a monotherapy in men progressing after chemo.
Valproic Acid (Depakote) is a well-known anti-epileptic and mood stabilizer that was recently discovered to have powerful anti-cancer effects. It and other HDACIs are in clinical trials against prostate cancer.
Valproic Acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
There is a clinical trial (NCT00670046) at Johns Hopkins of its use in men with PC progressing after treatment.
In human trials, the combination of valproic acid and an angiogenesis inhibitor (see angiogenesis inhibitor thread) has been safe and effective in several advanced cancers including PC.
Phase I study of anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers.
There is evidence from lab and animal studies that it may be most effective when combined with mTOR inhibitors (see mTOR thread)
• Synergistic effects of histone deacetylase inhibitor in combination with mTOR inhibitor in the treatment of prostate carcinoma.
• Impact of combined HDAC and mTOR inhibition on adhesion, migration and invasion of prostate cancer cells.
• Inhibitory effects of the HDAC inhibitor valproic acid on prostate cancer growth are enhanced by simultaneous application of the mTOR inhibitor Everolimus
Safety
Valproic Acid has been used in the treatment of epilepsy for almost 30 years. It exhibits several additional biological activities, in particular beneficial effects in migraine as well as side effects such as teratogenicity and, rarely, liver toxicity. It has only mild adverse effects in adults.