Think of energy metabolism as a party poop: Ripping something out late releases one stroke. Most of your cells are breaking apart to release "bang" of energy. Sometimes they rip off the fat, and in a pinch the cells can even metabolize protein.
Cancer cells make things a bit different. First, most cancer cells continue to depend on glucose, but switch from "cellular respiration" (which requires oxygen), to "glycolysis" (which may occur with or without acid). A study by the University of Colorado Cancer Center published today in the newspaper cancer Cell shows that stem cells from cancer take a third approach: they stick to cellular respiration, but switch from metabolizing sugar to metabolizing protein, or more precise amino acids, which are the building blocks of protein.
Healthy cells do not need to metabolize protein. The current study shows that cancer stem cells need to metabolize protein. And this difference turns out to be an Achilles heel that allows researchers to target cancerous stem cells without damaging healthy cells. The approach has already proven to be effective in clinical trials against acute myeloid leukemia and holds the promise for other cancers, including breast, pancreas and liver.
"In acute myeloid leukemia, we have become quite good at killing the majority of cancerous cells, but a small population of cancerous stem cells is uniquely equipped to resist these therapies, and these stem cells often survive to restart the condition later. We needed a way to specifically targeted at cancer stem cells, and it seems that this may be it, "said Craig Jordan, a doctor, investigator at the University of Colorado Cancer Center, Division Head of Division of Hematology and Nancy Carroll All Professor of Hematology at the University of Colorado School of Medicine.
In fact, Jordan has spent more than 20 years laying the scientific foundation for this cancer stem cell attack, and now only in the last six months, with a number of important publications, the work of his team has not only led to an increased understanding of These solid cells, but for treatments that can change the standard of care for acute myeloid leukemia and perhaps even other cancers. In a recent clinical trial, patients with acute myeloid leukemia who were not candidates for bone marrow transplantation with venetoclast have been treated, blocking the ability of the cells to absorb amino acids.
"Conventional chemotherapy is not effective for most patients with acute myeloid leukemia. The new results with venetoclax look very promising," said Jordan. Clinical test results are also published today in the journal naturopathy, with the first author Daniel Pollyea, MD. The current study recalls to indicate why the clinical trial was so successful.
In essence, a series of studies by first author Courtney Jones, Doctor and others in the Jordan Lab showed that leukemia stem cells do not (or may not) switch from cellular respiration to glycolysis like more mature cancer cells. Instead, they switch from metabolizing glucose to metabolizing amino acids – in fact, they depend entirely on metabolizing amino acids for energy, so much that when cells in the stamina's ability to absorb amino acids are interrupted, these cells die.
"Courtney's research is an important step in understanding how to better eradicate leukemia stem cells. With her result, I think we can now move on to create even more effective therapies," said Jordan.
The drug venetoclast stops leukemia stem cells from being able to use amino acids for energy. In the laboratory and now in the clinic, when researchers treated AML patients with venocock, leukemic stem cells. Important, since healthy cells are not dependent on amino acid metabolism, venetoclast kill leukemic stem cells without damaging healthy cells.
Interestingly, only AML patients treated with venetoclax were their first treatment, which showed such a dramatic response.
"When patients were treated with other therapies first, leukemic stem cells occurred to diversify and some assumed lipid metabolism," Jones said.
When these patients were later treated with venetoclax, the drug killed the cancer cells that continued to be dependent on amino acid metabolism but were ineffective against cancer stem cells that had switched to lipid metabolism. It was as if lipid metabolism provided space for these cells, and when even a small population of leukemic stem cells could resist therapy, they later re-started the disease growth.
The group's future work hopes to investigate the possibility of inhibiting lipid metabolism together with amino acid metabolism for use with AML patients whose cancer has resisted or recurred after previous treatments.
"In this document, we report an important part of science that describes the vulnerability of these leukemia stem cells, and in Natural Medicine Paper we describe a treatment that successfully exploits this vulnerability," said Jordan. "We believe that this kind of therapy is just the beginning of what can be a completely new way of treating leukemia. Now, our challenge is to optimize this treatment in acute myeloid leukemia, while expanding it to use in other settings where cancer stem cells continue to drive development, growth and relapse of cancer. "