Release date: 2015-07-24
According to the Science Daily, an article published in the Proceedings of the National Academy of Sciences refuted the common "variant accumulation" tumorigenesis model and supported another model that relied on evolutionary stress to affect cell populations. Essentially, this article states that healthy tissue ecosystems can make healthy cells out of cancer variability; but when tissue ecosystems change due to aging, smoking, or other stressors, cells with cancer variability suddenly become more Strong, making their group develop more than a few generations of natural choices.
New thinking about tumorigenesis has profound implications for cancer treatment and drug design. “We are trying to make drugs that target the mutations of cancer cells. But if the cancer is developing the body's ecosystem, not just the mutations caused by cancer, then we should give priority to interventions and life that increase the adaptability of healthy cells. Ways to choose to inhibit the emergence of cancer," said Dr. James DeGregori, senior research author, professor of biochemistry and molecular genetics at the University of Colorado School of Medicine, and associate director of basic sciences at the Cancer Center.
This new model helps answer a long-standing problem in cancer science called "Peto's Paradox" - if cancer is due to randomly activated mutations, then larger animals with more cells are The risk of developing cancer early in life should be greater. So why do mammals with different sizes and longevity develop cancer in the later stages of life?
"Blue whales have 1 million times more cells than mice, and their lifespan is 50 times longer than mice, but it does not have a higher risk of developing cancer in a lifetime than mice," De Gregory said. Andrii Rozhok, a colleague at De Gregory and Cancer Center, gave the answer that in addition to activating mutations, cancer also needs to undergo aging-related changes in the tissue to support cancer cells in healthy cells. Survival and growth during competition.
Consider the following two evolution scenarios: On a green meadow, the health of the grass is the best defense against dandelion; in the dinosaur era, the environment is very suitable for these giant lizards until the meteor impact, the new environment supports those who can better adapt to change The evolution of new species of the environment includes larger mammals.
Let's start with the lawn: “Healthy cells in the healthy body's ecosystem are optimal. But when the tissue ecosystem begins to change, such as aging or smoking, the mutations that cause cancer are very good at developing environmental conditions for damaged tissue groups. De Gregory said. In this scenario, De Gregory's advice is to develop interventions that support healthy tissue adaptation, which is like fertilizing grassland, rather than spraying weeds on weeds.
De Gregory's model is supported by studies that demonstrate that mutations that may cause cancer do not necessarily increase cell adaptability. “In fact, the healthy cells in the healthy tissue group are so optimized that almost any variation will lead to their reduced adaptability.â€
For example, certain cancer cells mutate in such a way that they can exist in an oxygen-deficient tissue environment that is common in the center of a developing tumor. But this adaptability only has an adaptive advantage in organizations with insufficient oxygen. This variation does not have this advantage in healthy, oxygen-rich tissues. In healthy tissues, cells with this mutation are lost in evolutionary competition with healthy cells, cancer cells are victorious, they die, or at least their population is suppressed, and the number is extremely small.
But when the organizational environment changes, what will it look like? This brings us back to the example of dinosaurs. 65 million years ago, the warm and humid earth supported the existence of dinosaurs, although there were still a few early mammals. When a huge meteor hit the Earth (and other environmental changes at the time), it changed the basic dynamics of the ecosystem. This adjustment of the ecosystem makes the furry, feathered, warm-blooded creatures ultimately dominate the Earth.
This looks like new successful genetic changes that have produced new, more successful species. But in the case of cancer, individuals with "new" genes may already exist, and confirming that ecosystem changes make them flourish. However, cancer biologists focus on cancer risk factors, such as how aging and smoking create new variability, rather than focusing on how these backgrounds change the tissue, thereby changing the choice of existing variability. De Gregory supports this view. He pointed out that the modeling study of stem cell pools shows that the selection pressure from the tissue group is stronger than the variation, which determines the composition of the stem cell population.
"But because of changes in the body due to aging, smoking, genetic differences in genetics, or other reasons, it changes the tissue ecosystem and allows new cells to replace healthy cells," De Gregory explained.
Of course, cancer development requires mutation and other genetic changes. But how do these mutations cause cancer? Perhaps these variations did not create an unexpected "super cell" that immediately "hacked and slayed". Tumor mutations often or always exist in the body, but have been pinned because of the pressure of choice. When the tissue ecosystem and its stress change so that cancer-varying cells are more likely to survive than healthy cells, the cancer cell population will defeat the healthy cell population.
We can avoid certain organizational changes caused by lifestyle choices, such as not smoking. Unfortunately, we cannot stop aging forever. But new therapies and new understandings can enhance some of the characteristics of the tissue group to better fight cancer for longer.
Source: Phoenix Technology
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