Mutations are necessary for cancer. But in his new book “Adaptive Oncogenesis: A New Understanding of How Cancer Evolves Inside Us,” James DeGregori, PhD, shows that mutations need help. The book sees the body as an ecosystem in which populations of cells compete and the cells best adapted to their surroundings survive. Healthy cells are best adapted to live in healthy tissue. But when tissues are damaged – for example, by aging, smoking or sun exposure – cells with cancerous changes may suddenly find themselves best adapted to their surroundings and may become able to out-compete healthy cells.
“This new theory, dubbed Adaptive Oncogenesis, which my lab has been developing for almost 20 years, represents a substantial departure from the current model of cancer causation in which risk factors like smoking or old age cause cancer by increasing the frequency of mutations. We instead propose that mutations may always be present, but the state of the tissue environment is the key determinant that either favors or disfavors cancer development – healthy youthful tissues favor normal cells over cells with cancer-causing mutations, while old or damaged tissues will be more likely to favor cells with cancer-causing mutations,” DeGregori says.
The implications of this theory are big: Rather than focusing our efforts on designing treatments to eradicate cells with cancerous mutations, DeGregori’s book shows that promoting tissue health helps normal cells out-compete cancer cells, keeping the body naturally cancer free.
And while we cannot avoid mutations as we age, we can develop interventions that alter tissue environments so as to disfavor cells with cancer-causing mutations.
“Just as crime is limited by fostering neighborhoods with better infrastructures and environments, we can limit cancer by engendering a healthier tissue landscape,” DeGregori says. In fact, DeGregori points out, everything that we already recognize as reducing cancer risk, from exercise to a good diet to not smoking, is also known to promote healthier tissues. Even for the cancer-promoting context that we cannot avoid, namely aging, DeGregori is optimistic that we will be able to develop preventative interventions that better maintain tissues, thus reducing cancer risk.
Just as Adaptive Oncogenesis influences our approach to prevention, these same ideas are applicable to cancer treatment.
“While many therapies are quite good at eliminating most of a patient’s cancer cells, advanced cancers typically relapse, coming back in a much more aggressive form that tends to resist therapy. We argue that the damaging effects of these therapies on the tissue environments leads to strong selection for cancer cells that can adapt to this drug-ravaged landscape, namely the nastier cancer cells,” DeGregori says.
He suggests that the field of cancer research should consider the impact of the therapy not just on cancer cells, but on the tissue environment as well.
“As such, we need to both develop therapies that are less damaging to normal tissues and interventions that can alleviate any damage that is created by therapies,” DeGregori says.
By providing a different perspective on cancer evolution, DeGregori hopes that this book will encourage students and researchers to think about cancer from a truly evolutionary perspective.
“While simple linear explanations of cancer (a mutagen causes a mutation, which causes cancer) have dominated for decades, the more ecological and evolutionary perspective offered in this book should provide a framework for better limiting the devastating impacts of this disease. I hope that this book will also encourage students and others to question dominant paradigms, to always search for evidence both for and against any particular theory, and to follow the data wherever it leads,” DeGregori says.
Adaptive Oncogenesis: A New Understanding of How Cancer Evolves Inside Us is available in many online bookstores. DeGregori will donate all proceeds from book sales, split between the Leukemia & Lymphoma Society and the V Foundation.