Can tumors undergo rehab?

So far I have discussed tumors at an organ level. Now let’s zoom-in one magnitude and understand tumors at a cellular level. Tumor is essentially an assortment of rapidly growing cells with diverse flavors of abnormality. Just like a normal cell, tumor cell also needs to carry out its ‘everyday business’ of maintaining its livelihood.

A normal cell has an elaborate yet efficient bureaucracy – depending on the context, recipes for specific proteins are decoded from the DNA into a decipherable RNA. Follow the directions contained in the RNA and voila you get a tailor-made protein! Depending on their function, proteins are then shipped to different areas of the cell; say to mitochondria – the energy house of the cell or to nucleus – the Washington D.C of the cell. Once proteins are at their assigned geographical locations, they relay external information through a defined grid that finally determines the fate of a cell – growth, stasis, aging or death. Notably, there are ‘ying’ proteins that negatively influence and ‘yang’ proteins that positively influence a cellular process. It’s the ratio of the ‘ying’ and ‘yang’ circuitry that finally determines the fate of a cell.

To accommodate for their exceptional rate of growth, an evolving cancer cell harbors several mutations in its genome and hence encoding abnormal proteins. One or more of these mutations may prove to be advantageous to the cancer cell in maintaining its ‘yang’ wiring. As a result tumor cells may become highly dependent or ‘addicted’ to one or more proteins. This phenomenon is called oncogene addiction. Since the abnormal protein(s) is the Achilles heel of tumor, then it is reasonable that removing it would at least impede, if not totally get rid of the disease. In fact, there is clinical evidence for it. For example, Glevec , a drug marketed by Novartis, targets a specific enzyme that a type of white blood cancer, called CML (Chronic Myeloid Leukemia) are addicted to. 95% of CML patients treated with Glevec had a disease free survival for five years – a remarkable achievement in cancer therapeutics.

Studies in mice have shown that different tumors undergoing the ‘de-addiction program’, via forced removal of the abnormal protein (say, protein A), react differently. Some tumors die, some just hang out without growing any further and some age. But as the theory of evolution suggests, a rare population of the original tumor that was insensitive to de-addiction, eventually repopulate – a case of tumor within tumor! This ‘new’ tumor is not addicted to protein A, but may now be heavily dependent on protein B. So theoretically it would respond to protein B de-addiction regime. So the bad news is that there may not be one wonder drug that can cure the tumor completely. But the good news is that a cocktail of drugs may be more effective at keeping aggressive tumor growth at bay…and I believe that we are on the right path to find the right mix :)