Lessons from Ecology to Oncology: How to Manage Invasion

There is one thing that I share with almost every person I’ve ever met; cancer has impacted our lives in some way or another. Cancer is the second leading cause of death world-wide. In 2016, an estimated 1,685,210 people will be diagnosed with cancer in the United States alone, with 595,690 of who are expected to die from the disease. Because of these frightening statistics, oncologists have tried countless aggressive therapies, each focusing on the complete eradication of the disease. This strategy has been the therapeutic equivalent of a huge bombing of an entire area just to hit one house, and has yielded little progress in the field. In fact, aggressive chemotherapies and gene-targeting treatments may even create the selective environmental pressures that promote metastasis or promote outgrowth of resistant cells. This suggests that the key to success in cancer research lies not in a more aggressive offensive attack, but in a more practical offensive strategy. Robert A. Gatenby (2009) suggests an alternative approach to cancer treatment utilizing ecological concepts pertaining to invasive species in his paper “A change of strategy in the war on cancer”.

           

Gatenby’s work examined the progression of an invasive species, the diamondback moth. Once established in Illinois, the diamondback moth spread throughout all of North America within five decades. Aggressive chemical treatments decreased population sizes only briefly, and eventually led to biologists finding strains resistant to all known insecticides. Sound similar to aggressive cancer treatment? Ecologists’ management style has progressed beyond the “large bombing for a single house” method and moved towards precision. This movement to ‘integrated pest management’ strategies have been implemented for controlling diamondback moth populations, as well as hundreds of other invasive species. Integrated pest management focuses on restricting population growth rather than completely eradicating the population. Gatenby (2009) then suggests that these same pest management strategies can be directly applied to cancer. The invasion of pests involves dispersal, proliferation, migration and evolution. These same four stages are also considered the major mechanisms of cancer metastasis. Cancer also appears to respond to environmental pressures similarly to the diamondback moth, in that eradication attempts resulted in both populations producing highly resistant strains. Furthermore, there are more cancerous cells in 10 grams of tumor tissue than there are people on Earth, making it unfeasible to eliminate the entire population. With this information in mind, Gatenby (2009) sought to apply methods of controlling invasive pests to methods of controlling cancer progression.

Patterns of cancer progression in mouse models strongly support Gatenby’s proposal of ecological modeling. His models show that drug-sensitive cancer cells will proliferate at the expense of less fit, drug-resistant cancer cells in the absence of therapy. However, when a large portion of the drug-sensitive cells are killed, for instance by eradication therapies, the drug-resistant cells can proliferate unconstrained. In contrast, mice with ovarian cancer that were treated with a drug dose continuously adjusted to maintain a stable tumor volume survived longer than mice treated with the traditional chemotherapy. With these findings as support, Gatenby (2009) suggests that cancer research should deploy treatment methods that maintain a stable tumor volume, which could increase a patient's survival by preventing the outgrowth of inherently resistant cells.

           

Although the ecological concepts discussed in this paper are extremely important for the field of cancer research, there is still much work to be done before they can be effectively put to use. I would like to expand upon Robert A. Gatenby’s ecological take on cancer metastasis by proposing somewhat of a conceptual renaissance for both ecological modeling and the field of cancer research. I propose that ecologists and oncologists alike exhaust a wide range of scientific concepts while designing methods for controlling an invasive species, rather than focusing on the immediate short-term effects of any one treatment. Tumor cell metastasis can be modeled as the migration of an invasive species caused by the micro-environmental pressures of aggressive drug treatments. The types of environmental cues that enable a tumor cell to metastasize are similar to those that enable invasive species to migrate and occupy different environments. Identifying the pressures that cause tumor cells to develop migration abilities would allow researchers to manipulate drug applications in a way that creates a homeostatic tumor environment. Doing so would prevent tumor cells from experiencing the micro-environmental pressures that enable them to metastasize. Successfully limiting cancer metastasis through the manipulation of these cues could provide great insight to ecologists attempting to prevent invasive species from dominating landscapes, and most importantly provide new hope for those seeking a cure to this deadly disease.

 Reference

Gatenby, R. A. (2009). A change of strategy in the war on cancer. Nature, 459 (7246), 508-509