As we learn more from the cancer genome project and therapeutic strategies that provide long-term benefits, what types of targets might allow us to do better? Many successful cancer therapies directly or indirectly damage DNA, and many target replication in some way. Whereas kinase and other inhibitors can show strong initial impacts, resistance seems to be a greater problem with some types of inhibitors. Should we be aiming for drugs that rapidly kill cancer kills but may cause resistance by strong selective pressure or those that weaken cancer cells but better avoid resistance.
Actually when a cell passed from various mis-happening ( like mutaions and dysfunctioning in repair sytem etc) then it can possibly transformed into a cancer cell. This cell is immortal in nature and have self-sufficiency to grow and protect itself by ownself. The reason of its mortality hides in its signaling system, which is powerful and chaotic and because of its chaoticness it is not easily targettable. Although if u succeed in targeting to one of the factor, it will shift its signalling from this factor to some other mechanism more probably the one which is in cross talk with this factor. therefore selectivity and resistance comes into the picture.
Basically targeting in cancer is dependent on two governing factor. 1) expression of the target (protein and enzyme) in cancer cell in comparison to the normal cells. 2) Shape of its substrate binding site and conformation of that active site.
lets take an example of kinase family which are highly express in cancer.
And there are 518 protein kinase which uses ATP for their signalling. So in this case the molecule (ATP) is same but it structural conformation are different for every receptor.
So the researcher pick this point and that's how they get selectivity for one kinase. In other words the developed kinase inhibitor will bind in such a way that is only suitable to for only one kind of active site of kinase not on the other kinase ATP binding site.
So answer of your question, It is very terrifying to say the chances of getting an optimal target (protein) in cancer is negligible. So we have to follow the receptor based or ligand based drug discovery approach for development of anti-cancer drugs to make them more selective against the cancer.
Although no one knows when new novel discovery in this field, change the fate of whole chemotherapy against the cancer!!!!!
We need to understand mitogens TNF and apoptisis inducing factors in a wide perspective of hematopoiosis to unlock the anigma of cancer biology
I think you're totally right. It seems logical to treat cancer with those drugs which cancer cells have limit potential to induce resistance against them. But the major problem as you somehow indicated, is genome instability of these cells. Any drug category has its own pathway to function and cancer cell can switch to some alternative pathways to lower the drug effect. I personally think that the best way to combat the cancer cells is to use the body's own potential. Some kind of treatment which trigger the immune responses and potentiate this system will work more efficiently I believe. But the great results will achieve when there is enough time to work for immune responses. In this regard some prophylactic strategy like using cancer vaccine may work properly.
You may want to investigate research conducted/ written by Dr. Douglas Swartzendruber (Indiana University, Indianapolis) and Dr. Kenneth Pennington (Goshen Cancer Center). Dr. Pennington currently has a cancer vaccine in clinical trials.
I wonder if allosteric targets for proteins such as kinases might prove a better long term strategy than trying to block the ATP binding sites which will obviously have strong similarities and require drugs to compete against 1 mM concentrations of ATP inside cells.
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