Friday, June 7, 2013

Cancer is a sine qua non for life as we know it.


There was a post today on National Geographic talking about a tumor that was found in a fossilized Neandertal's bone. It reminded me that I had written the piece below and hadn't found a home for it yet. The title, which is a big jarring, is:

Cancer is not a disease: there is no cure.

The way we describe things shapes and is shaped by the way that we think of them.  Cancer has been described as a disease for as long as we have written record of medicine.  It’s name comes from the greek word for crab, because the way it wedges itself into the host tissue is so like a crab wedges itself between rocks: inextricably.  


The advent of the microscopic age at the turn of the 20th century brought with it an unprecedented view of the cellular level; anatomy and pathologies came into a new focus and a new science was born: microbiology.  As physicians, we were offered a new opportunity to study diseases at the cellular level, to describe the panoply of new patterns that we saw under the microscope much like a team of explorers coming into undiscovered jungle filled with undescribed flora and fauna.  We found that the cancers in each organ were not necessarily the same.  Indeed, we found a rich diversity of cancers that could be reliably classified and whose prognoses and patterns of progression correlated.  This richness of classification gave rise to the opportunity for disease specific treatment trials, and indeed accounted for most of our progress against these individual entities, and for the standard of care for most cancer types even today.  


The dawn of the genomic age, first with the human genome project, and then with the cancer genome atlas, promised and delivered another wave of discovery and deeper, more detailed classification.  Just as we can now tell how, and when two species of finch, or cave fish, diverged in their evolutionary history, so too can we tell when and how a tumor diverged from its tissue of origin.  Early on in this story, we were tantalized by the discovery of specific genomic errors (mutations) that seemed to explain a cancer’s growth, and with the discovery of imatinib, a targeted ‘cure’ for a specific cancer (CML), and cancer seemed to be on its knees, ready to be cured.  


The final cure, however, has continued to elude us.  As we continue to discover more and more specific mutations, drug companies continue to develop specific drugs to target their action.  Each of these drugs seems to work well in a subset of patients, for a time, but never provides the silver bullet that we have been promised, and ultimately fails in almost every case.  The problem is that we are stuck in a paradigm where each disease has a cause, and each cause has a remedy.  This linear thinking has dominated medicine, and indeed much of science, for most of human history, and has served us well.  But continuing to think of cancer as a disease in this paradigm is not going to get us any closer to a cure - we have to shift our thinking and expectations, and embrace the reality that cancer is the result of a non-linear, highly degenerate process, and therefore has no 'cure'.

We have to shift our focus in the study of the cancer genome and stop trying to develop a comprehensive list of errors in the code that cause cancer, but instead learn the guiding principles behind the process - the equations of motion, if you will.  Cancer is not a disease to be cured, but a pathologic condition of normal tissue evolving according to the very rules which allowed us to emerge from the primordial ooze.  It is an inconvenient sine qua non for existence in our universe, as evolving, living organisms.  

This reclassification is not intended to take anything away from those living with cancer, or who have suffered from it.  Within any single patient, this pathologic condition has the capacity to cause as much, or more, suffering than does any other disease.  And, as oncologists, our calling is to minimize this suffering, and when we can, cure our patient.  But until we stop thinking about cancer as a disease that is the product of a linear process, and realize that it is a pathologic condition that is produced by any number of trajectories across an evolutionary landscape; until we stop looking for a single, silver bullet cure for all patients that doesn’t exist, we will continue to waste time that we could be using to understand the evolutionary dynamics of cancer so we can develop strategies to cure each patient.



Some further reading:


Exploiting ecological principles to better understand cancer progression and treatment
arXiv preprint
Basanta and Anderson


Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective.

Huang et al.  2009 Sep;20(7):869-76. doi: 10.1016/j.semcdb.2009.07.003


Oxidants, antioxidants and the current incurability of metastatic cancers.

Jim Watson,  2013 Jan 8;3(1):120144. doi: 10.1098/rsob.120144.