Cancer cachexia│Japanese research: Revealing “cancer cachexia”, one of the key causes of cancer death, is expected to improve the survival rate of patients with advanced cancer.

Cancer cachexia│”Cancer cachexia” is a common complication symptom of advanced cancer patients, and it is also the direct cause of death of many cancer patients. A Japanese study found that the Netrin protein secreted by cancer cells is involved in causing systemic symptoms of cancer. By inhibiting Netrin factor, it will not affect cancer cells immediately, but it can effectively improve the survival rate of cancer individuals, or it may become a treatment for cancer caused by cancer. A new target for systemic symptoms.

Written by: [email protected] Inspire 医．Thinking │ Image source: aslysun＠Shutterstock, CI [email protected], Nutnutchar [email protected] │ Source: International scientific journals《The EMBO Journal》、RIKEN

Cancer cachexia│Japanese research: Revealing “cancer cachexia”, one of the key causes of cancer death, is expected to improve the survival rate of patients with advanced cancer.

Cancer cachexia is a common complication in patients with advanced cancer, and it is also the direct cause of death in many cancer patients. The research team led by Sa Kan Yoo, a researcher of the dynamic homeostasis research team of the Life Function Science Research Center of RIKEN, found that the Netrin protein secreted by cancer cells is involved in triggering systemic symptoms of cancer, by inhibiting Netrin Factors do not affect cancer cells immediately, but can effectively improve the survival rate of cancer individuals, or may become new targets for the treatment of systemic symptoms caused by cancer.

The team has published the research results in the European Molecular Biology Organization journal “The EMBO Journal” on May 4, Japan time.

cancer cachexia

Cancer cachexia is a common complication of cancer patients, that is, a condition in which muscle and fat are significantly depleted by the naked eye. Affected by factors such as hormonal and metabolic disorders in cancer patients, or reduced food intake, they may experience weight loss, muscle atrophy, decreased activity, fatigue, anorexia, satiety, lethargy, anemia, emaciation, blood sugar Instability, decline in quality of life, and adverse effects on medical prognosis, etc., but even with general nutritional support for its treatment, it is difficult to change the patient’s symptoms.

Cachexia can be observed in many patients with advanced cancer, although it is especially common in patients with advanced gastrointestinal cancer and lung cancer, but in fact the occurrence and severity of symptoms are not completely related to the type, location, size, extent and stage of the tumor. It is one of the leading direct causes of death in cancer patients. Some clinicians pointed out that cancer cachexia makes patients very weak. In clinical practice, the cause of death of many cancer patients is not from the cancer itself, but from cancer cachexia. According to foreign research statistics, non-cancer deaths of cancer patients are as high as 40%.

Research purpose and method

As the cancer progresses, the patient’s body will begin to fall into a state of cachexia, which has adverse effects on organs far away from cancer cells, and even the whole body, which is very unfavorable for the prognosis of the disease. However, the detailed mechanisms by which localized cancers cause systemic symptoms and adversely affect individuals remain unclear. In order to understand the basic mechanisms that cause these systemic symptoms, the research team created an experimental cancer animal model in fruit flies. Among them, Ras is an oncogene important for regulating cell proliferation and one of the oncogenes commonly mutated in different types of cancer. The researchers expressed the mutated Ras gene in the eye tissue of Drosophila larvae, Making cancer cells appear in the eye discs of fruit flies. Finally, it was found that even though the cancer cells in the eye discs of adult fruit flies did not metastasize or proliferate in large numbers, more than 80% of the individuals died within a few days after the cancer was induced.

Based on the results, the researchers hypothesized that “it may not be the cancer cells themselves, but the factors secreted by the cancer cells that have adverse effects on the whole body.” After comprehensive analysis of RNA Sequencing (RNA-Seq), 20 secreted factors were identified that were upregulated in the eye discs of Drosophila with cancer cells, and the genes that secreted factors in cancer cells were analyzed. Inhibition to investigate its effect on organism viability. They eventually settled on Netrin secretory factor, a secreted protein that induces axon growth and is found in nematodes, flies and mammals.

The study found inhibitionNetrinFactors can effectively improve the survival rate of patients

The team found that when the Netrin factor in cancer cells is inhibited, although it has no effect on the growth of cancer cells themselves, it can improve the survival rate of cancer-affected individuals and significantly increase the survival rate of individuals.

After conducting a detailed analysis of the Netrin factor, the team found that the Netrin factor produced by cancer cells inhibits the production of a substance called carnitine in fat tissue away from cancer cells, thereby reducing the amount of carnitine in the entire individual. content. Since carnitine is essential for fatty acid metabolism, which converts intracellular fatty acids into energy, it has been suggested that reduced levels of carnitine can lead to low or even insufficient energy in the body, leading to death in the individual.

The team later tried to improve the survival rate of individuals by improving the systemic symptoms caused by Netrin factors. The researchers inhibited Netrin receptors and their downstream signals in fat body tissues far away from cancer cells. It was found that a significant increase in the level of carnitine led to a significant increase in the survival rate of cancer individuals. In addition, the researchers found that administering carnitine or acetyl-CoA (acetyl-CoA) produced by carnitine to individuals lacking carnitine due to cancer can also restore the survival rate of cancer individuals.

The team believes that the individual’s death can be effectively avoided by controlling systemic symptoms

The researchers believe that the discovery that Netrin, an axon-attracting factor, is associated with cancer cachexia is of great significance, because it has long been known that the levels of Netrin in the blood and urine of cancer patients are elevated and detected in their blood. The two phenomena have been considered to be seemingly unrelated. The Drosophila cancer model used in this research has the potential to become a model that reflects the cachexia physiological state of cancer patients.

Another important significance is that the research shows that even if the cancer cells themselves are not changed, the death of the individual can be avoided by changing the metabolic state of the tissues away from the cancer cells. This result suggests that it may be possible to improve patient survival by controlling systemic symptoms even in the presence of cancer, or may become a new target for the treatment of systemic symptoms caused by cancer.