Thursday, April 5, 2012

The Evolving Tumour

Some people wonder why the challenge of cancer has not been met. Even with the advanced techniques of today the principle strategy for defeating cancer remains personal behavior. The treatments are improving but at a slow rate. This news item highlights that despite all we have learnt about cancer at the molecular level, there are some very important information that we simply fail to discover. Fortunately with so much research going on the representations we can create are increasingly accurate, much more detailed, and slowly but surely coalesce into fruitful schemas that facilitate the development efficacious therapies. This news item calls for a some serious reconsideration of our strategic imperatives.

A tumour can be a hotbed of diversity, British scientists have discovered. Just as different types of tumours have distinct genetic mutations, so do separate parts of the same tumour.

Please be advised I have no empirical means by which to understand this phenomenon. I can conceive of some vague inaccurate, lacking in detail and contradictory approaches to the problem but that never stopped me speculating. So I'll share those but read with the understanding that these are only educated guesses and those aint worth much.


One of the remarkable findings of stem cell research is how a stem cell, all other things being equal, can differentiate into different cells types simply because of the shape of the receptacle into which it is placed. We have no way to understanding this at present. It highlights how geometry seems to figure so prominently in life processes. Some mathematical biologists have been playing around with that for quite some time. The research is very nascent, long way to go, but it could point to one causal factor driving the tumoural diversity because tumours do not grow in a regular pattern. It is one factor to look for in skin cancers. Moles typically grow nice and round, one that is breaking symmetry could well be cancerous. So as a tumour invades space it is encountering different geometric arrangements.


Because tumours create their own blood vessel supply differing areas of the tumour may be receiving differing humoral factors because parts of the tumour may be tapping into a blood supply from a nearby organ.


Vascular density probably varies throughout the tumour. So some cells can create ATP through aerobic glycolysis and if enough oxygen is present electron transport chain ATP production. Other cells will rely predominantly on anaerobic glycolysis. These alternative ATP production pathways(there are others) change genetic signatures. For example, in cancer cells glycolysis relates gene transcription can be very much elevated. Metabolic changes of this nature tend to have associated effects on gene transcription.


The whole tumour environment may enable pre-cancerous cells that were previously attacked by NK cells to survive because many tumours create an immunosuppresive signal. See my previous post. Particularly given the prevalence of aneuploidy in cancer cells it may be the case that there are intrinsically very high rates of mutation and what we see in large tumours are the survivors in that frenetic somatic evolutionary event.

That's enough of my nonsense. It is a fascinating problem, one that is fun to think about, but it does present some very worrying clinical implications.


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