Environmental biologists have studied it for years – cancer biologists are just starting to think about it – and it has the potential to result in a fundamental change in our understanding of cancer. I am talking about ecosystems.
We all learned in elementary school that diversity helps an ecosystem thrive. Bees need flowers so they can make honey from the nectar. Flowers need bees for pollination. Neither would be able to exist without each other.
How does this concept apply to cancer? Our traditional view of cancer is that cancer cells within a tumor are the same. One cell starts growing out of control, pushes out the normal cells, and the result is cancer. Indeed, we talk about cancer as being “monoclonal,” i.e. all cells being the same. A major goal of cancer research over the past decade has been to understand the changes in genes that drive the monoclonal growth of cancer cells. In some cases, such as chronic myelogenous leukemia and some cases of melanoma, we have identified the gene that causes the cancer to behave badly, and have been able to treat the cancer successfully by targeting the product of the rogue gene.
However, cancer has proven to be much more complex at the genetic level than originally thought. We now know the monoclonal theory is not the whole story. Cancer cells within a single tumor are not all the same. Indeed, most cancers contain multiple “clones” even within a single tumor mass. They may have started from a single cell, but by the time they are detected, they are composed of cells with remarkable genetic diversity. Each tumor, unexpectedly, is genetically diverse.
There is solid research demonstrating that even after a cancer has developed, additional mutations occur that can provide one cancer cell a growth advantage over its surrounding cancer cells, thereby allowing those cancer cells with the additional mutation to grow faster (or spread more easily). These cells with additional mutations are genetically different from the cancer cells around them. As they outpace the growth of other cancer cells in the tumor, the result is genetic diversity within that tumor.
There is an alternative explanation that is only now being considered. If confirmed, this alternative explanation could change how we think about cancer and cancer therapy. It is related to – you guessed it – ecosystems. It may be that a tumor actually represents an ecosystem of cancer cells, with different cancer cell populations playing different roles.
For example, suppose a person has a small, slow growing tumor that doesn’t progress because it is being suppressed by the immune system and also has a limited blood supply. The person doesn’t even know it is there. Then, some of the cells in the tumor have additional genetic changes that make a hormone that supports growth of new blood vessels into the tumor (so the tumor can get nutrients) while other cells in the tumor develop different genetic changes that block the immune system from rejecting the tumor. A tumor containing both types of cells will have a growth advantage over a tumor that does not have both types of cells. It will be able to both get more nutrients and also avoid the immune system. In essence, such a tumor will be strengthened by its diversity. It can then grow, spread, and become a full blown cancer.
What does this mean for cancer therapy? In nature and society, we celebrate the strength that comes from diversity. The opposite is true for cancer where the goal would be to cause the onco-ecosystem to collapse. Indeed, if such onco-ecosystems exist, it means that we may not have to target each and every cancer cell in a tumor. A treatment that works on one key type of cell within the tumor might cause the whole onco-ecosystem to collapse, thereby resulting in regression of the tumor. Furthermore, if we can identify the specific changes in a subset of cells that are necessary for a robust onco-ecosystem, perhaps we can detect them earlier or even prevent them.
This is all still theory, but very recently, collaborating teams of environmental biologists (who previously did not think of their work as cancer-relevant) and cancer researchers (who had not thought about ecosystems in many years) are developing and testing new models based on this theory. Once again, we have an example of how we are strengthened by the diversity of our scientific ecosystem. Hopefully, this scientific ecosystem will provide the clues to how we can cause collapse of the onco-ecosystem, thereby leading to new approaches to cancer prevention, detection and therapy.