In 2017, researchers Iñigo San Millán, from the University of Colorado Springs, and George Brooks, from the University of Berkeley, published the hypothesis that lactate played a very important role in the development of cancer. In fact, San Millán and Brooks stated at the time that lactate was the only metabolic component present and necessary in all stages of cancer.
In their hypothesis, the scientists explained the Warburg effect for the first time. This effect was discovered by Nobel laureate Otto Warburg in 1923 and associated excess lactate in the body with cancer . However, the reason for that presence was not known. San Millán and Brooks discovered that lactate was produced to develop cancer.
Researchers have continued working in this line and have managed to prove their hypothesis: the accumulated lactate (the one related to cancer) activates the main mutated genes involved in the growth and proliferation of cancer. “In fact, if these mutated genes are not exposed to lactate, they have a difficult job of causing cancer. For example, last year’s Nobel Prize went to three researchers for their work on the transcription factor HIF-1 which, when mutated, is a fundamental element in the development of many cancers. It is not yet very clear what triggers HIF-1 production in cancer. In our study we have discovered that lactate directly regulates the expression of HIF-1 between 290-480% ”, tells us San Millán.
The results of the new study were recently published in the journal Frontiers in Oncology . In this research the scientists exposed human cancer breast cells to glucose and lactate was produced. This increased the expression of all the major mutated genes involved in breast cancer by 150-800%.
Now, San Millán and his team are replicating this study in other cancers such as small cell lung and non-small cell lung. They are finding results similar to breast.
But what exactly is lactate or lactic acid? How does it work? What produces it? Let’s go by parts … Lactate is a product that is obtained from the combustion of glucose (either obtained from the food we eat , or from the mobilization of glycogen stored in the muscles and liver ) and that cells consume for energy. What’s more, lactate is one of the major sources of energy for cells. It should be noted that the brain and the heart are two of the great lactate consumers in our body.
On how lactate works, San Millán sums it up: “The dynamics of lactate is very stable in general. It enters cells and is converted into energy but does not accumulate. However, in cancer, some of that lactate is converted to energy, but most of it is constantly accumulating at the site where the tumor occurs. What we have discovered is that this accumulated lactate is essential for tumor growth since it activates the main mutated genes involved in the growth and proliferation of cancer ”.
When we exercise we also produce lactate , which could lead us to think that with its practice we would be fueling cancer. Well, there is nothing to fear because as the Spanish researcher tells us, the lactate that we manufacture while we run, play football or pound ourselves in the gym does not accumulate but is converted into energy and disappears from the muscle in minutes. In addition, this lactate creates positive responses to improve performance and fitness . “However, lactate in cancer constantly accumulates, it is not” recycled “and as we have shown it is” deregulated “and begins to activate the genes involved in cancer to continue their function of transforming normal cells into cancer cells. , as well as for the growth and proliferation function of the tumor ”, he explains. So now you know, exercise adapted to the personal conditions of each one and under medical supervision is good.
Another question that arises about lactate is whether by reducing our intake of sugar and carbohydrates, we would limit the amount of glucose in our body and with it the possibility of lactate being produced. The answer is complicated. To begin with, the more aggressive cancer is, the more glucose it needs and if this is not available, it will steal it from the body and the muscles. By stealing glucose from the muscles , cachexia, that is, the loss of muscle mass, can occur in cancer patients. Again, the more severe the cancer, the greater the need for glucose and the more cachexia it causes. So that we understand each other, the muscles would eat themselves to produce the glucose that the disease requires . “Therefore, care must be taken to restrict carbohydrates in cancer patients as it could accentuate cachexia in many of them. I am finishing a study with cancer patients with the MD Anderson hospital in Houston (the number 1 in the world in cancer) and indeed, we are seeing that patients with more advanced cancer and cachexia have significantly less glycogen than patients without cachexia and cancer-free patients. Much research is still needed in this regard. I am not saying that you have to increase glucose consumption at all, but that restricting carbohydrates in states of cancer could be dangerous ”, points out the Spanish researcher.
The San Millán and Brooks team is now trying to block lactate and decrease its production. “If we manage to block lactate, we would end cancer since it would run out of its ‘visa’ or ‘passport’. The problem is that all cells consume and produce lactate and if we systemically block lactate, it would most likely be lethal. Therefore, we are focusing on trying to exclusively block the lactate present in tumors. At the moment, in breast cancer cells as well as lung cancer, we are seeing an in vitro reduction in the proliferation and survival of these cancer cells of between 60-85% in just 48 hours. Now we have moved to the in vivo phase, we have implanted these tumors in mice and we have begun to study the evolution of these tumors. We are already developing new approaches to reach the tumor in a localized way and block lactate, although like all research it takes time to prove it and then to be a successful therapy ”, concludes San Millán.
