1000% increase in chemotherapy efficiency with prozac!
 

Prof. Rimona Margalit, found that Prozac enhanced doxorubicin's efficacy more than 1,000%. Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it..


http://www.medicalnewstoday.com/articles/133784.php


They have not tested with BC chemo drug but they seem to expect that it could potentially work accross a range of chemo drugs

Wow! That could make a lot of patients err..happy. I know valproic acid, another mood mgt drug/anti-epileptic is supposed to be helpful but...1,000%? Again..wow!
If the the mechanism isn't anything specific to Dox, this would be tremendous. Even if just for Dox, could mean a lower dose could be used for desired effect with less toxicity. And if case histories are analyzed, results shouldn't take long to confirm.
An emerging liposomal encapsulated Doxo should be less toxic to begin with. Studies have suggesetd following it 24hrs later with Zoledronate greatly enhances effect..but posibly only in ER-.
So....why haven't we heard more about this?

A discussion:
http://scienceblogs.com/bushwells/20...ancer_drug.php

Another article about conflict with Tamoxifen:
http://www.smh.com.au/text/articles/...708350568.html

Suggesting Prozac has anticancer properties by itself:


1: Cancer Biol Ther. 2008 Oct;7(10):1685-93. Epub 2008 Oct 22.http://www.ncbi.nlm.nih.gov/corehtml...ioscience2.jpg Links
Fluoxetine inhibits the extracellular signal regulated kinase pathway and suppresses growth of cancer cells.

Stepulak A, Rzeski W, Sifringer M, Brocke K, Gratopp A, Kupisz K, Turski L, Ikonomidou C.
Department of Pediatric Neurology, Children's Hospital, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Dresden, Germany. andrzej.stepulak@uniklinikum-dresden.de
Fluoxetine (FLX) is a widely prescribed antidepressant. Concerns were raised about the potential impact of FLX on cancer growth, because FLX was shown to promote development of breast cancer in rodents. Here we studied the effect of FLX on tumor growth in lung (A549), colon (HT29), neuroblastoma (SKNAS), medulloblastoma/rhabdomyosarcoma (TE671), astrocytoma (MOGGCCM) and breast (T47D) cancer cells and explored potential mechanisms of its action. In our study, FLX reduced growth of cancer cells in vitro in a concentration dependent manner. The antiproliferative effect of FLX was already evident after 24 hours exposure and more pronounced at 96 hours. We demonstrate that FLX inhibits phosphorylation of ERK1/2 kinases in a time and concentration-dependent manner, followed by reduced phosphorylation of transcription factor c-Myc in A549 and HT29 cells. After treatment with FLX, A549 and HT29 cells demonstrated concentration-dependent decrease in the expression of c-fos, c-jun, cyclin A, cyclin D1, and increased expression of p21(waf1) and p53 genes, which resulted in slowing of the cell cycle progression. We suggest that these changes could be responsible for observed inhibition of cancer cell proliferation during FLX treatment in vitro.
PMID: 18836303 [PubMed - indexed for MEDLINE]

Interesting. I was put on prozac after chemo, as a SSRI
inhibitor to help me sleep. I wonder if it made a difference with the Adryamicin I took just weeks before?

Thank for the extra search Rich, Yes why do we not hear more about it? well I have my own theories, just like why do we not hear more about Yamanoto's experiments..

Anyhow it would have to be taken at the same time than chemo (chemo is only active for few hours and the rest of the time your body is dealing with the side effects). Some patient are on prozac when receiving cancer treatments so we already know that it should be safe. I am not advising on anything I am just informing.

HMMMMMM

Very interesting....should be an easy one to get "off label"!

Anyone pursuing this?

this is interesting news!!! take care of cancer and the depression we get for having cancer all at the same time!!!

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Is there anything new on this?

Re: 1000% increase in chemotherapy efficiency with prozac!
 

1: Cancer Lett. 2009 Feb 8;274(1):118-25. Epub 2008 Oct 11.http://www.ncbi.nlm.nih.gov/corehtml...PubMedLink.gif Links
Treatment of resistant human colon cancer xenografts by a fluoxetine-doxorubicin combination enhances therapeutic responses comparable to an aggressive bevacizumab regimen.

Argov M, Kashi R, Peer D, Margalit R.
Department of Biochemistry, Tel Aviv University, Tel Aviv 69978, Israel.
Pre-clinical studies of multidrug resistance (MDR) usually address severe resistance, yet moderate MDR is already clinically-impeding. The purpose of this study was to characterize moderate drug resistance in human colon cancer, and it's modulation by fluoxetine. In vitro fluoxetine enhanced doxorubicin's cytotoxicity (10-fold), increased doxorubicin's intracellular accumulation (32%) and decreased efflux of intracellular doxorubicin (70%). In vivo, mild treatment with a doxorubicin-fluoxetine combination slowed-down tumor progression significantly (p<0.001 vs. doxorubicin alone), comparable to aggressive treatment with bevacizumab. Collectively, our results suggest that combinations of fluoxetine with chemotherapeutic drugs (P-glycoprotein substrates) are worthy of further pursuit for moderate MDR in the clinic.
PMID: 18851896 [PubMed - indexed for MEDLINE

Re: 1000% increase in chemotherapy efficiency with prozac!
 

So...not only a chemo helper..possibly a resistance reverser. I'd love to know the treatment success for chemo patients on prozac and metformin(diabetics).

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Hmm, I'm wondering if this has had an effect on me. I've been on prozac for nearly ten years. So far, I'm doing well since all my chemo and herceptin. This is very interesting.

Re: 1000% increase in chemotherapy efficiency with prozac!
 

This study

http://www.prozactruth.com/cancer.htm

talks about the antidepressants that can actually double the risk of breast cancer. Interesting.

Dianne

Re: 1000% increase in chemotherapy efficiency with prozac!
 

I had someone say to me once (a doctor, laughingly) that they should just put Prozac in the water. What's the phrase, Prozac, its not just for breakfast anymore!

I took it religiously during treatment, it helped tremendously with the depressive effects of chemo (which had me reduced to a weeping mess). I go on and off it now, but mostly because the economy has me so depressed!

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Based on more recent research, overall..doesn't look they increase risk

2005
1: Epidemiology. 2005 Jan;16(1):101-5.http://www.ncbi.nlm.nih.gov/corehtml...ges-pmlogo.gif Links
Breast cancer risk among users of antidepressant medications.

González-Pérez A, GarcÃ*a RodrÃ*guez LA.
Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain. agonzalez@ceife.es
BACKGROUND: Breast cancer is the most common cancer in women. Laboratory studies suggest that antidepressants may promote breast cancer tumor growth. Several epidemiologic studies have evaluated this association with conflicting results. METHODS: We conducted a cohort study with a secondary nested case-control analysis based on the General Practice Research Database. Our goal was to assess the association between the risk of breast cancer and use of serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other antidepressants. We calculated adjusted estimates controlling for breast cancer risk factors using unconditional logistic regression. RESULTS: A total of 3708 cases of breast cancer were ascertained. Overall, antidepressant use was not associated with an increased risk of breast cancer. Current users of SSRIs had an odds ratio (OR) of 0.98 (95% confidence interval=0.81-1.19), whereas current users of TCAs had an OR of 0.86 (0.73-1.00). When only use for longer than 1 year was considered, the corresponding estimates for SSRIs and TCAs were 0.76 (0.53-1.09) and 0.87 (0.70-1.09), respectively. None of the individual drugs was associated with breast cancer risk. CONCLUSIONS: Use of antidepressants was not associated with an increased risk of breast cancer regardless of duration of use, daily dose, or specific drug being used. These results, together with evidence from prior studies, support the lack of a clinically meaningful association between breast cancer risk and antidepressants.
PMID: 15613952 [PubMed - indexed for MEDLIN



2006
http://www.dslrf.org/breastcancer/co...id=132&cid=598

and

1: Breast Cancer Res Treat. 2006 Jan;95(2):131-40. Epub 2005 Dec 2.http://www.ncbi.nlm.nih.gov/corehtml...ringerlink.gif Links
Antidepressant use and breast cancer risk.

Chien C, Li CI, Heckbert SR, Malone KE, Boudreau DM, Daling JR.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. cchien@fhcrc.org
BACKGROUND: Antidepressants are among the most commonly prescribed drugs in the United States. Laboratory studies suggest that because certain antidepressants increase prolactin levels that they may also increase breast cancer risk. However, human studies evaluating use of antidepressants in relation to breast cancer risk have yielded inconsistent results. METHODS: A population-based case-control study consisting of 975 breast cancer cases 65-79 years of age diagnosed from 1997-1999 and 1007 age and residence-matched controls was conducted in western Washington State. Detailed information on antidepressant use was obtained through structured in-person interviews. Logistic regression was performed to analyze the relationship between antidepressant use and breast cancer risk. RESULTS: Overall, there was no association between ever use of antidepressants and breast cancer risk (odds ratio [OR] = 1.2, 95% confidence interval [95% CI]: 0.9-1.6). When evaluated separately, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), and triazolopyridines were each not associated with breast cancer risk. However, risk varied by hormone receptor status. Compared to never users, ever users of SSRIs had elevated risks of progesterone receptor (PR) negative and estrogen receptor (ER) positive/PR-negative breast cancers (OR = 1.8, 95% CI: 1.1-3.6 and OR = 2.0, 95% CI: 1.1-3.8, respectively), but not of tumors with other hormone receptor profiles. CONCLUSIONS: Based on these results and those of previous studies, there is limited evidence that any type of antidepressant use is associated with breast cancer risk overall. SSRIs may elevate risks of PR- and ER+/PR- tumors, though further studies are needed to confirm these associations.
PMID: 16322894 [PubMed - indexed for MEDLINE


1: Expert Rev Neurother. 2006 Sep;6(9):1363-74.http://www.ncbi.nlm.nih.gov/corehtml...line100x25.gif Links
Review of the epidemiological literature on antidepressant use and breast cancer risk.

Coogan PF.
Slone Epidemiology Center, Boston University, MA, USA. pcoogan@bu.edu
Based on evidence that antidepressants increase levels of prolactin and may promote the growth of mammary tumor cells, there has been concern that the use of these drugs may increase the risk of breast cancer. This article reviews the epidemiological evidence on the relationship between breast cancer risk and the use of the selective serotonin reuptake inhibitors, the tricyclic antidepressants and other antidepressants. Overall, the evidence does not support the hypothesis that the use of antidepressants increases the risk of breast cancer. There is a dearth of data on long-term selective serotonin reuptake inhibitor use. Since these drugs are commonly used, it is prudent public health policy to monitor breast cancer incidence among women using this class of drug for long durations.
PMID: 17009923 [PubMed - indexed for MEDLINE


2008
Links
Anti-depressants not linked to increasing risk of cancer.

McCord A.
PMID: 19048675 [PubMed - indexed for MEDLINE]
no abstract available


2009
1: Pharmacoepidemiol Drug Saf. 2009 Jul 21. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/corehtml...nce_150x34.gif Links
Antidepressant use and colorectal cancer risk.

Coogan PF, Strom BL, Rosenberg L.
Slone Epidemiology Center at Boston University, Boston, MA, USA.
PURPOSE: A previous epidemiologic study reported a 30% reduced risk of colorectal cancer among users of high doses of selective serotonin reuptake inhibitors (SSRIs). We assessed the association of colorectal cancer risk with SSRI and tricyclic antidepressant use in our hospital-based Case Control Surveillance Study. METHODS: For the SSRI analyses, we used data collected on 529 colorectal cancer cases and 1955 hospitalized controls collected from 1995 to 2008. For the tricyclic antidepressant analyses, we used data on 2889 cases and 7122 controls collected from 1976 to 2008. We used multivariable logistic regression analysis to evaluate the association of regular SSRI use and regular tricyclic antidepressant use (daily use for at least 3 continuous months) with colorectal cancer risk. RESULTS: The odds ratio for regular SSRI use was 0.55 (95% CI 0.35-0.88) and it did not differ by duration of use. The odds ratio was 0.47 (95% CI 0.26-0.85) for colon cancer and 0.72 (95% CI 0.37-1.41) for rectal cancer. The odds ratio for regular use of tricyclic antidepressants was 0.77 (95% CI 0.52-1.16) CONCLUSIONS: We found an association of reduced risk of colorectal cancer with regular use of SSRIs. In light of laboratory data indicating that SSRIs may inhibit colon cancer and one previous epidemiologic study that also observed a decreased risk, further investigation of the effect of SSRIs on the risk of colorectal cancer is warranted. Copyright (c) 2009 John Wiley & Sons, Ltd.

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Well, I would urge caution here. The jury is still out if you read the statement I copied from one of the articles. Are these studies funded by any drug companies? No bias?
Dianne

'SSRIs may elevate risks of PR- and ER+/PR- tumors, though further studies are needed to confirm these associations.
PMID: 16322894 [PubMed - indexed for MEDLINE'

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Here's a related thought. Current research shows that antipressents, such as Paxil, Prozac and Zoloft, "are part of a class of drugs that inhibit CYP2D6, an enzyme that converts tamoxifen to its active form."

Therefore, taking these antidepressants concurrently with tamoxifen might reducing the estrogen inhibitor's effect.

The results of trials were given at the spring ASCO meeting.

Joan

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Seems like there is a fair amount of more recent supportive research by different entities in different countries.
Yeah..definitely some info on conflict with Tamoxifen. Have not heard this in regards to aromatase inhibitors or fulvestrant.

It might also be relevant that risk before diagnosis is very different than efficacy once already diagnosed. Kinda apples and oranges. Eg. Soy and Flax are generally thought to be BC preventive but may be forbidden once diagnosed.

Who pays for the studies is always a potential issue..with just about everything prescribed. But then..with the cost and risk of failure, I wonder how many helpful pharmaceuticals would be available if only disinterested parties funded the multiphase trials necessary for approval.

Re: 1000% increase in chemotherapy efficiency with prozac!
 

What about taking depressants, such as Ativan or Valium? Any studies on these drugs and their interaction with chemo, herceptin, AI's or Tamoxifen?

I just learned about this CYP2D6 enzyme and will ask my doc about it before and if I begin Tamoxifen. But I'd be interested in learning what my anti anxiety drugs have been doing while I've been on these other drugs (Taxotere, Carboplatin -finished in March, 09, continuing with Herceptin until Oct. 8 -17 tx's.)

Dianne

Re: 1000% increase in chemotherapy efficiency with prozac!
 

I think that's why it's important to get tested with the CPY2D6 metabolizer test to see if you metabolize Tamoxifen poorly, intermediate, normal or hypermetabolize. The dosing for Tamoxifen would be individualized based upon how you metabolize the drug. Genelex can do the test as well as Mayo. Genelex charges $295 which may be covered under some insurance.

Dianne

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Well my 2 cents..

Why would there be a multimillion pound trials for a product that is already approved with many generic one available..it would not be cost efficient for any pharmaceutical company to undertake me think.

As I said chemo is just active for few minutes/hours at bestafter IV so really I think it would just be a matter of taking prozac perhaps just few days before or perhaps just during chemo treatments, what ever you feel may be appropriate.

I would not venture into trying other forms that the one we have data for, what would be the point. As to interaction with tamoxifen well as explained before it would not be taken for long. And as a matter of fact there is a debate as to whether one should take inhibitors during chemos..

As I said before I am not advising simply putting the info and my thoughts out there..

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Sure about the short active time-frame of chemo? Intuitively, it would seem much longer given that nadir is usually a week out or so for typical chemos. And the recent Dox followed by Zometa info suggests at least 24 hours separation for benefit.
Regardless, however it works, seems like benefits of this combo should be pursued. To start with, how about everyone ask their oncs about it?

Re: 1000% increase in chemotherapy efficiency with prozac!
 

Pretty sure (but will try to find out where I read this to confirm). I remember thinking the same as you did when reading the info and being surprised too. But no it is broken down quickly by the body (defending itself) and the weeks that follow chemo is used to deal with the cellular damages and metabolites created (which we associate with chemo action but it is in fact chemo effects).

Well indeed 24h separation is not long in any case..

And indeed again if you in the USA have onconlogists that are ready to sit down and take the time to read this and are open to suggestions and progressive then yes it would be great to ask!

And there is no counter indication for you to use it then it seems that there is little to be lost..IMHO

Re: 1000% increase in chemotherapy efficiency with prozac!
 

HDACs, thought to help defeat cancer stem cells, compared to Fluoxetine.

A recent paper in the Journal of
Neuroscience has shown that inhibitors
of histone deacetylases (HDACs)
— enzymes that affect the acetylation
status of histones and regulate the
remodelling of chromatin — have
antidepressant actions.
Although currently used antidepressants
rapidly modulate
mono aminergic systems in the
brain, the emergence of their moodelevating
effects requires several
weeks of administration, which
suggests that altered gene expression
is involved in antidepressant action.
So, compounds that modulate
the epigenetic regulation of gene
expression, such as HDAC inhibitors,
might have antidepressant actions.
Nestler and colleagues used a
mouse model of chronic social defeat
to investigate histone acetylation in
depression and the effect of HDAC
inhibitors in the nucleus accumbens,
which is a brain region implicated in
the development of depression and
antidepressant action.
Immunohistochemical analysis
showed that, although acetylation
levels of histone H3 at lysine
residue 14 (acH3K14) decreased
transiently by ~50% 1 hour after
the final stress event, there was an
increase at 24 hours and 10 days.
Expression levels of HDAC2, but
not of HDAC1 or HDAC3, were
decreased 24 hours and 10 days after
the final stress event, suggesting that
this could mediate the increase in
acH3K14 levels. A similar increase
in acH3K14 levels, accompanied
by a decrease in HDAC2 levels,
was present in postmortem
samples
of the nucleus accumbens from
depressed humans.
Infusion of the HDAC inhibitors
vorinostat (a class I and II HDAC
inhibitor) or MS275
(a class I
HDAC inhibitor) into the nucleus
accumbens of mice that were
subjected to chronic socialdefeat
stress reversed stressinduced
social
avoidance and increased the amount
of time that the mice spent socially
interacting. In forcedswim
tests,
which are often used as an acute
screen for antidepressants, both
inhibitors showed antidepressantlike
effects but had no effect on anxietylike
behaviour.
As chronic socialdefeat
stress
leads to distinctive patterns of gene
expression in the nucleus acumbens,
which can almost be normalized by
fluoxetine treatment, the authors
tested the effects of MS275
on gene
expression using microarray analysis.
Like fluoxetine, MS275
mostly
reversed stressinduced
genomic
changes, and both fluoxetine and
MS275
treatment caused similar
changes in the expression patterns
of many genes. The regulation of
certain genes by chronic stress
was reversed by MS275
but not
fluoxetine, which might reveal new
targets for antidepressant action.
These included genes encoding gap
junction membrane channel protein
α5 (which is involved in gap junction
formation), discs largeassociated
protein 1 (which assembles postsynaptic
density complexes) and
the α1αadrenergic
receptor.
So, although selectivity and
delivery issues remain to be resolved,
HDAC inhibitors, which are in
clinical trials for cancer indications,
might also have therapeutic potential
in depression.
Charlotte Harrison
ORIGINAL RESEARCH PAPER
Covington, H. E. et al. Antidepressant actions of
histone deacetylase inhibitors. J. Neurosci. 29,
11451–11460 (2009)
FuRtHER REAdING Kazantsev, A. G. &
Thompson, L. M. Therapeutic application of
histone deacetylase inhibitors for central
nervous system disorders. Nature Rev. Drug
Discov. 7, 854–868 (2008)
MOOd dISORdERS
Antidepressant action
through gene regulation
ReseaRch highlights
NATurE rEvIEwS | Drug Discovery voLuME 8 | NovEMbEr 2009
© 2009 Macmillan Publishers Limited. All rights reserved

Re: 1000% increase in chemotherapy efficiency with prozac!
 

I've been real depressed lately, I wonder if I should give it a whirl? Maybe I will talk to the Doc next Thursday.

Re: 1000% increase in chemotherapy efficiency with prozac!
 

rich66 - i am curious about what you wrote on this subject about valproic acid (depakote). i happen to be on it and would like to know what effect, if any, it has on chemo. thank you. valerie

Re: 1000% increase in chemotherapy efficiency with prozac!
 

On this thread..still waiting to for Dr. Peer to release more helpful data regarding Prozac/Chemo synergy.

On Valproic acid and chemo,
Possibly quite helpful.

I posted some abstracts on HDAC inhibitors and benefit against presumed cancer stem cells. HDACs may also reduce resistance to endocrine therapy. It very well may depend on the exact combinations used. But these would be good items to mention to your onc:


Histone deacetylase inhibitors as a new weapon in the arsenal of differentiation therapies of cancer.

Botrugno OA, Santoro F, Minucci S.
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Absent or altered differentiation is one of the major features of cancer cells. Histone deacetylases (HDACs) play a central role in the epigenetic regulation of gene expression. Aberrant activity of HDACs has been documented in several types of cancers, leading to the development of HDAC inhibitors (HDACi) as anti-tumor drugs. In vitro and in vivo experimental evidences show that HDACi are able to resume the process of maturation in undifferentiated cancer cells, justifying their introduction as differentiating agents in several clinical trials. Modulation of cell fate by HDACi is observed at several levels, including the stem cell compartment: HDACi can act both on cancer stem cells, and with the rest of the tumor cell mass, leading to complex biological outputs. As a note of caution, when used as single agent, HDACi show only a moderate and limited biological response, which is augmented in combinatorial therapies with drugs designed against other epigenetic targets. The optimal employment of these molecules may be therefore in combination with other epigenetic drugs acting against the set of enzymes responsible for the set-up and maintenance of epigenetic information.
PMID: 19345000

1: Clin Cancer Res. 2009 Apr 1;15(7):2488-96. Epub 2009 Mar 24.http://www.ncbi.nlm.nih.gov/corehtml...nres_final.gif Links
Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: phase I/II trial of valproic acid and epirubicin/FEC.

Munster P, Marchion D, Bicaku E, Lacevic M, Kim J, Centeno B, Daud A, Neuger A, Minton S, Sullivan D.
Division of Hematology Oncology, University of California, San Francisco, Divisadero, San Francisco, California 94143-1711, USA. pmunster@medicine.ucsf.edu
PURPOSE: The aim was to study the biological and molecular effects of the histone deacetylase (HDAC) inhibitor, valproic acid, in patients with solid tumor malignancies. EXPERIMENTAL DESIGN: A phase I dose escalation of valproic acid given on days 1 to 3 followed by epirubicin (day 3) was followed by a dose expansion of valproic acid combined with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC100). Pharmacodynamic and pharmacokinetic studies entailed valproic acid and epirubicin plasma levels and their interaction, the effects of valproic acid on histone acetylation in peripheral blood mononuclear cells (PBMC) and tumor cells at baseline and day 3, and baseline expression of HDAC2 and HDAC6 as therapeutic targets. RESULTS: Forty-four patients were enrolled in the phase I part, with a disease-specific cohort expansion of 15 breast cancer patients (median age, 55 years; range, 28-66 years) receiving 120 mg/kg/day valproic acid followed by FEC100. Partial responses were seen in 9 of 41 (22%) patients during the phase I part. Objective responses were seen in 9 of 14 (64%) evaluable patients at the dose expansion with a median number of 6 administered cycles. Predominant toxicities were valproic acid-associated somnolence and epirubicin-induced myelosuppression. Valproic acid plasma levels were associated with short-term, reversible depletion of WBC and neutrophils within 48 hours. Histone acetylation in tumor samples and in PBMCs correlated with valproic acid levels and was further linked to baseline HDAC2 but not to HDAC6 expression. CONCLUSION: Valproic acid is a clinically relevant HDAC inhibitor, and PBMCs may serve as a surrogate for tumor histone acetylation in solid tumor malignancies. HDAC2 should be further considered as a relevant therapeutic target.
PMID: 19318486

J Mammary Gland Biol Neoplasia. 2009 Mar;14(1):45-54. Epub 2009 Feb 28.
Resistance to endocrine therapy: are breast cancer stem cells the culprits?

O'Brien CS, Howell SJ, Farnie G, Clarke RB.

"A common theme of many investigations into CSCs is that they have inherent resistance to chemo and radiotherapy. This is proposed to be due to mechanisms such as more efficient DNA damage checkpoints and survival pathways compared to more differentiated tumor
cell populations."

"Enhanced interaction between estrogen receptor signalling and growth factor tyrosine kinase pathways such as EGFR, HER2/erbB2 and IGFR mediates resistance to endocrine therapy"

"HDAC inhibitors are being used in a number of on going clinical trials including a phase II trial evaluating vorinostat in ER positive patients with metastatic breast cancer who failed prior aromatase inhibitor therapy and up to three chemotherapy regimes [95]. A report of preliminary findings presented at ASCO 2008 showed that out of the 17 enrolled patients 21% had a partial response and 29% had stable disease after treatment with vorinostat 400 mg daily for 3 of 4 weeks and tamoxifen 20 mg daily,
continuously. These findings suggest that the addition of an HDAC inhibitor to tamoxifen in patients who have failed prior aromatase inhibitors or adjuvant tamoxifen may restore hormone sensitivity."

Re: 1000% increase in chemotherapy efficiency with prozac!
 

hm. they're experimenting with only 120 mgs.... i take 1250! maybe i have some valproic acid whammo to back up my chemo! wouldn't *that* be nice. i already loved the fact that it just happens to also stop migraines, which i had before and which have now disappeared. a triple bennie med. thank you for the information. valerie

Re: 1000% increase in chemotherapy efficiency with prozac!
 

120 mg/kg/day is a weight based dose equation, not actual dose. 1kg = 2.2 lbs. So they were administering roughly 60mg for each pound of patient presenting. You are either very petite or getting lower dose http://acronyms.thefreedictionary.com/MG%2FKG%2FDAY