Last weekend, I attended the American Association for Cancer Research (AACR) conference on Metabolism and Cancer. This meeting was a three-day immersion in a topic that, even after over 20 years as a cancer researcher, was sometimes enough to make my head spin. Fortunately, sharper minds than mine are chipping away at the almost overwhelming complexity to reveal the secrets of how tumors grow, spread, evade our immune system and become resistant to treatments. The bottom line is: it’s complicated.
As a succession of researchers and clinicians presented their research and revealed the myriad ways by which cancer cells overcome the metabolic limitations that would, ordinarily, limit their growth, I couldn’t help thinking of the over-simplified “cures” that are so often promoted in the lay press and social media. The alkaline diet, ketogenic diet, DCA (dichloroacetic acid), are all proposed by their backers, as cure-alls through their purported impact on metabolism. Ironically, there is some biological plausibility deeply buried in each of those, often over-stated, claims. Some are even being tested for their ability to enhance conventional therapies by making cancer cells more vulnerable to those treatments. However, like many conventional therapies, these proposed alternative cure-alls are not enough, in themselves, to prevail against cancer.
Research on the impact of lifestyle factors on cancer cell metabolism is at a relatively early stage, but diet, physical activity and body fatness all have substantial impacts on our metabolism. Understanding how best to apply those factors and, in which patients, is a rapidly expanding focus of research.
Cancer cells – adapt and thrive
The foundation of all proposed metabolic approaches to cancer therapies is the theory that cancer cells are more restricted in the types of fuel that they can use, compared to normal healthy cells. By extension, starving the tumor of its preferred fuel or making it more difficult for cancer cells to use that fuel, will stop cancer in its tracks while sparing normal cells that can use other fuels. Unfortunately, cancer cells can be exquisitely adept at activating ways to exploit other available fuel sources. The metabolic programs that cancer cells activate to overcome these hurdles are not new; the instructions for these mechanisms are already coded in our DNA. These mechanisms have evolved to enable us to develop from embryos, to sustain us during starvation, to repair us after injury or protect us from infection. Cancer cells merely hijack these programs to perpetuate their growth at the expense of the patient.
Scavenge and survive
Probably the most striking statement of the conference, for me, was “if you can scavenge it, you don’t need to synthesize it,” said, Dr. Aimee Edinger, Associate Professor at University of California, Irvine. Cancer cells can become the ultimate scavengers, even exploiting the destruction of neighboring cancer cells by treatments, as a source of fuel and building material for further their own growth. This means that treatments that target a single pathway or cellular fuel may produce an initial response but be prone to the development of resistance to that therapy. However, treatments that use combination approaches may overwhelm the adaptability of cancer cells and deliver the knock-out punch.
Another theme of the meeting was that cancer metabolism is not merely a passive passenger, swept along by the genetic chaos of a cancer cell; metabolism drives the behavior of cancer cells. Metabolism can reprogram cells, protect cancer cells from immune attack and ultimately control the fate of the tumor and the patient. Consequently, therapeutic and lifestyle approaches designed to adjust the metabolism of cancer cells (and their surrounding microenvironment) may provide a way to both change the biology of the tumor and to make them more amenable to available treatments.
In many ways, the traditional perception of cancer as an exclusively genetic disease created a binary view of its treatment; the only option was to destroy the rogue cells…or not. However, if changing the metabolic environment can impact the trajectory of disease and engineer vulnerabilities, metabolic approaches will increasingly be part of the strategy for both cancer treatment and prevention. Research on the impact of lifestyle factors on cancer cell metabolism is at a relatively early stage, but diet, physical activity and body fatness all have substantial impacts on our metabolism. Understanding how best to apply those factors and, in which patients, is a rapidly expanding focus of research.