The Maw of the Beast

I come from a Physics background, and before coming to Sage had never given any thought to the problem of cancer treatment before.  Looking at the marvel that is the human organism, it was previously my assumption that no cell could survive massive insertions, deletions or substitutions in its code.  In fact, I assumed that the difference between cancer cells and normal cells was a single mutation in a promoter region or in some signalling protein.  Certainly, based on the degree of genetic similarity we see in humans, the cells in this complicated organism that slowly evolved over millions of years couldn't survive a complete reorganisation of its genome... right?

So wrong.

I was reading "The Biology of Cancer" by R. A. Weinberg, and looking at Figure 1.11 is looking into the maw of the beast.  They had fluorescent probes such that each of the human chromosomes would show up as a different color in a normal cell, and then applied the probes to a cancer cell.  The original genome was so jumbled up in the cancer cell that it wasn't even clear what chromosome each piece might have been in the first place!

In fact, cancer cells evolve just like their very own organism.  While the original defect might be a point mutation, the tumor evolves through several phases before finally becoming a rapidly-spreading malignancy.  The evolution diverges so dramatically that part of a tumor may respond to a drug and part may not!  To really drive home the point of how different the cancer cells have become versus normal cells, cancer cells may not even metabolise food in the same way that normal cells do! 


So, that brings me to why there's no cure yet.

• The cancer is constantly evolving to evade whatever assault from the immune system or drugs you apply to it.  Because of its enhanced rate of growth and its loss of DNA repair mechanisms, two hallmarks of cancer, it can evolve resistance to treatments as fast as any pathogen.
• Your normal cells have evolved a complex web of regulatory interactions over the millions of years that led to your existence.  Even if we had the life-saving treatment for a cancer on the shelf among all of the available chemotherapy treatments, we may have a very hard time determining which one to give the patient because of the number of things that are available to go wrong with cells!
• The tumor evolved in a unique environment:  your body!  In its evolution, the cancer may have learned how to exploit the correctly-functioning mechanisms of nearby tissues in order to further its proliferation.  So, if the normal cells are part of what's going wrong, then breaking the cycle of malignancy may necessarily involve toxicity to your normal tissues!

These are challenges that I had never considered before coming to Sage, but they're also things that we're working on.  Cheap gene sequencing may be able to give us access to biomarkers that were previously invisible.  Every month more papers on the body's regulatory networks are released and better analysis methods are developed.  Further, amid these myriad things that can go wrong, as a Physicist who loves generality, I can cling to one absolute amid a phylogeny of complex modes of failure:

• Cancer is always a regulatory failure.

By understanding gene regulation, we can understand cancer.  By understanding it, we can start bringing better treatments to patients.