Hi,
I am trying to study the synergistic effects with our compound and other anticancer drugs. I have been successful with compounds such as Sunitinib, Paclitaxel and Pazopanib but I am failing for other compounds. But, even for these compounds I have found synergistic effect only at certain specific concentrations. For other concentrations, there is no synergistic effect and sometimes the compounds seem to oppose each other. For eg: Sutent (10 um) with compound (10 um) show synergistic effect at but when concentration of Sutent decrease and concentration of our compound increases there is no synergistic effect. I tried 9 compounds and found synergistic effect with only three.
Can someone suggest on a effective strategy on synergistic effect. My strategy so far has been to use concentration of drugs which are lower than IC50 and a bit higher concentration for my drug than its IC50. IT worked for three compounds but not for others. Any suggestions?
It is not so simple to say that combining 2 cancer drugs will instantly provide you with "synergistic" effects.
There must be some rationale behind the combination.
For example for the 3 compounds that is successful for you, sunitinib and pazopanib are tyrosine kinase inhibitors while paclitaxel is a microtubule stabiliser. The mode of action is different, and it is quite difficult to pinpoint the biological rationale of the combination.
there are many review articles on polypharmacology which explain the rationale behind certain combinations, but most of the time too little is known about the biology to accurately predict these "synergistic effects".
I'd recommend you read Chou and Talalay's paper, "Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors", https://doi.org/10.1016/0065-2571(84)90007-4. They both develop a relatively robust and commonly used definition for synergy, go into some detail for why it works and is better than some other methods, and give a reasonably straightforward step-by-step procedure for how to do the experiment.
That being said: part of the trick is that one actually expects that synergistic drugs may only synergize at some concentrations, but not others. That's why it's useful to do full dose curves, rather than single point experiments - it gives a better idea for what will happen over a full range of treatment options.
- Badges
- Science topic