Prediction of Synergistic Drug Combinations for Prostate Cancer by Transcriptomic and Network Characteristics
Prostate cancer (PRAD) is a major cause of cancer-related deaths. Current monotherapies show limited efficacy due to often rapidly emerging resistance. Combination therapies could provide an alternative solution to address this problem with enhanced therapeutic effect, reduced cytotoxicity, and delayed the appearance of drug resistance. However, it is prohibitively cost and labor-intensive for the experimental approaches to pick out synergistic combinations from the millions of possibilities. Thus, it is highly desired to explore other efficient strategies to assist experimental researches. Inspired by the challenge, we construct the transcriptomics-based and network-based prediction models to quickly screen the potential drug combination for Prostate cancer, and further assess their performance by in vitro assays. The transcriptomics-based method screens nine possible combinations.
Although the therapeutic effect of cyproheptadine in Prostate cancer has never been reported, the use of cyproheptadine in the treatment of multiple malignancies, such as myeloma, leukemia and hepatocellular carcinoma, to some extent suggest the effect of cyproheptadine in combating cancers. Therefore, it is reasonable for cyproheptadine-containing combinations to be potential for the Prostate cancer treatment.
Cyproheptadine represents an attractive anticancer drug candidate, especially as it is already in clinical use as an anti-serotonin and appetite stimulant and is well tolerated and officially approved for years.
Serotonin is a growth factor for several human carcinomas, glioma and carcinoids. Serotonin is also involved in cancer cell migration, metastasis and angiogenesis. The levels of the monoamine in the tumor play a crucial role in cancer progression. Serotonin receptor expression becomes dysregulated in several cancers.
bopnk..thanks for bringing up this interesting issue of anti cancer effect of a very old drug, Cyproheptadine. Cyproheptadine used to be over the counter remedy for cold and cough in USA. Then, for some unknown reason FDA removed it from OTC list.Doctors still prescribe Cyproheptadine for making children and elderly gain weight. It can cause 10lbs to 40 lbs weight gain within 3 months of use. (bad side effect for men on ADT)
Cyproheptadine is also used to counter sexual side effects of anti depressant meds.
Other than weight gain and sleepiness. .other side effects are not common.
Did not come across anti cancer effect articles about Cyproheptadine...do you have any research studies?
On a side note...Anti depressants like Sertraline, Imipramine, Phenelzine etc are now known for slowing growth of prostate cancer...even killing stem cells. Serotonin connection of Prostate cancer is a new and fascinating area.
Do you think it would be a good idea for my dad to try to get a depressant prescribed as a supplementary therapy or would normal doses just not work? I've read some studies on anti-depressants for prostate cancer and some of them seemed like high doses?
Anti depressants meds ,SSRI type.. keeps anxiety lower, anger and irritability lower, mood and sleep better . Besides that there are many reports that they have anti cancer effect. Something to discuss with his Doctor.
This is the first study demonstrating an overexpression of serotonin receptor subtypes 1A and 1B in prostate cancer cells, especially in high-grade tumors. Moreover, serotonin stimulates proliferation of prostate cancer cells and 5-HT1A receptor antagonists inhibit proliferation.
Cyproheptadine is also a antagonist of the 5-HT1A receptor.
Some SSRI drugs are actually selective serotonin receptor antagonists. Prozac is the most famous one, being antagonist on 5-HT2C receptor, which probably explains most of its antidepressant effects.
Of the SSRI type of antidepressants Bupropion seems to be the one called out for potential lessening of ADD (ADHD) symptoms.For me it would be 2 birds with one stone.
Yes...there are a few anti depressant meds which are used as second line drugs for ADHD/ADD. Prominent ones are Bupropion (wellbutrin) and Venlafaxine (effexor)You are right anti depressant meds lowering mental side effects of ADT.. they keep mood stable and anxiety lower. One other benefit is their weight loss effect in men who eat too much ..particularly high carb foods. Anti depressants certainly reduce or even eliminate hot flashes caused by ADT. Prostate cancer guys should look into multiple benefits anti depressant meds have.
Thanks. Yep I just now replied to my reply at the same time you sent this.2 1/2 years into ADT etc. and it's about time I get serious about anti-depressant. It's not so much about a true depression but cognitive decline.
I still get a kick out of one of us here a year ago or so who said "If you're diagnosed with stage 4 cancer your first prescription should be for an antidepressant". With an exclamation mark.
I check all the boxes for ADD from online tests and had a light bulb moment 10 or so years ago when I realized the abbreviation ADD referred to me lol.
When I was growing up no such term. Instead the notations at the bottom of report card "he looks out the window all the time" "he doodles all the time" "he's a daydreamer".
It occurred to me that I am the same in my adult life.
Anyway.....
So I see 2 or 3 benefits from Bupropion (Wellbutrin) for example.
There is a lot to this it appears. As someone said probably best to see a Psychiatric professional Dr,This excerpt alone points to me that my mental state that I can't seem to accurately describe has been defined by the medical community ( I fit anhedonia ).
Individuals who experience anhedonia lose interest in common activities, but in ways that are distinct from dysphoria. Unlike dysphoria, anhedonia is characterized more by the lack of feelings than depressed feelings. These symptoms can be divided into physical and social anhedonia.
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