In my encounters with cancer biology as a researcher I have always had a nagging feeling that our focus has been somewhat off target. Cancer cells are evolution in action, which is why it is such a difficult disease to treat. There is a great degree of variation within and between tumors. Cancer cells are replication machines that rapidly adapt to their environment. Cancer is on my mind even more than usual because over the past few years friends and relatives have been battling this disease.
A recent paper (See reference below) probes the deep evolutionary origins of the survival program employed by cancer cells. It is a compelling idea and this paper surveys the prior work and extends it. This view characterizes cancer as not only a new species but as a separate kingdom than the ancestor/host organism since it has moved from being part of a multicellular organism to being a parasite that operates at a single cell level.
This characterization rings true in the description of cancer cells as a single celled organism adapted to Pre-Cambrian conditions and pursuing a replication strategy of “any-cost cellular survivalism.” This perspective is consistent with the capacity of cancer cells to survive and even thrive in conditions of hypoxia (low oxygen). This has many implications for the treatment of cancer because the primary therapeutic strategies like radiation and chemotherapy resemble the harsh environmental threats faced by our ancient ancestors when this survival program arose. So it is no wonder that many cancers remain viable after treatment and the surviving lineages often become even more robust after such challenges.
In the original context this survival program could provide an escape hatch or lifeboat for a single cell from the constraints of being part of a multicellular organism. Basically the cell adopts an “every cell for itself” mentality when the going gets tough as a strategy to insure cellular survival. As multicellular organisms further evolved the control mechanisms to inhibit the defection of cells became stronger but not insurmountable. In the ancient aquatic environment it was possible for the survivalist cell to make a go of it on its own. However the current endgame of cancer is the death of the host it is overrun by unchecked proliferation of the cancer cells. With some notable exceptions being the rare cases of cancers becoming a transmissible disease as is the case for a facial cancer in Tasmanian devils or being selected as a standard laboratory strain like HeLa cells (http://en.wikipedia.org/wiki/Henrietta_Lacks).
In order to implement this strategy as a heuristic replicator the cancer cell jettisons regulatory programs required for good citizenship in a multicellular organism. Rapid mutation rates and genomic instability allow the cancer cell lineage to quickly explore configurations for optimal survival and replication as a parasite.
This view of the cancer cell as an artefact of evolutionary history is both encouraging and discouraging. This perspective is consistent with the limited success that we have achieved in decades long “War on Cancer”. Our current paradigm to challenge cancer cells with harsh regimens also wreaks havoc with the rest of our body. However it is heartening that there are aspects of this survival program that may expose vulnerabilities of cancer which could be exploited to derail the survival program. For example, low oxygen levels appear to drive more aggressive tumor behaviors including metastasis. A focus on increasing oxygen levels in the core of tumors is a promising avenue for further research.
Bioessays 34:72-82 (Mark Vincent, 2011).