How to deal with cancer drug resistance - (Jun/11/2011 )

Anybody has a good idea on how to solve cancer drug resistance issues. Many new drugs are designed to block one or more signal transduction pathways in order to block cancer cell proliferation. But cancer cell can bypass the blocked pathway and survives later in the treatment cycles.

Combination or coktail of multiple drugs can have serious side-effects. What other general ideas can provide better solutions on drug design and cancer treatment.

Hola there is a phenomenom knwon as multidrug resistance MDR in cancer responsible of that. you know?, Buena suerte

protolder on Mon Jun 13 06:17:57 2011 said:

Hi Protodler, sorry to reply late. Your answer went to a different question. The question I asked is how to deal with cancer cell resistance due to cell rescue by alternative pathways. MDR-based drug resistance is mainly caused by cell membrane molecule-delivery mechanism if I'm correct.

Right now, many drugs are developed to block one or few signal transduction pathways. Cancer cells can survive by complementary pathways. How we find a way to prevent cancer cell self-rescue? That's my question.

There is one hypothesis from my lab about how drug resistance occurs in HIV-1 protease and HCV NS3/4A protease - the Substrate Envelope Hypothesis. I don't really know much about cancer drugs and cancer in general but the hypothesis is that the viral substrates that the proteases occupy share a conserved space and whenever a drug, however potent it is, pierces that conserved space, drug resistance occurs.

If you want to learn more about drug resistance in HIV-1 protease and HCV NS3/4A protease, please read the publications from my lab - Celia Schiffer's lab in UMass Medical School. Maybe there is something applicable to cancer as well, because there are parallel mechanisms in drug resistance that we saw in Influenza, antibiotic resistance and fungal resistance.

Other than that, there are few groups who are working on coping with the resistance issue by not directly perturbing the active site of a protein but trying to find molecules that will allosterically inhibit the target molecule. You can also search their strategies on to how to cope with drug resistance.

Cheers

There are several reasons leading to drug resistance, such as altered targets, MDR or action of complementary pathways.
for different reasons, combination therapy with different inhibitors seems to be effective.