When babies born less than one year ago were diagnosed with cancer that seriously threatened their lives, it was undoubtedly a bolt from the blue for the whole family. However, it is puzzling that the symptoms of some of the children will change miraculously: Without treatment, the tumors in their bodies will disappear by themselves.
These children suffer from a very dangerous and common tumor—— Neuroblastoma 。 This is the most common extracranial solid tumor in infants, and 15% of infant cases caused by cancer are caused by neuroblastoma.
The origin of this kind of tumor can be traced back to embryonic development, and it forms in undifferentiated sympathetic ganglion cells. Therefore, neuroblastoma may occur in the adrenal gland, spine, neck, chest and abdomen, where there are sympathetic ganglia. Subsequently, the tumor can metastasize to multiple parts of the body and develop resistance to chemotherapy.
▲ Aggressive neuroblastoma cells gather in tissues (picture source: reference [2]; Credit：Frank Westermann/DKFZ）
As a result, For a considerable number of high-risk children with neuroblastoma, it is difficult to effectively control the tumor for a long time even if they receive high-intensity treatment. Many children were killed by cancer before they could feel the beauty of the world.
However, among children with neuroblastoma, there are a small number of lucky ones. Even if they do not receive any treatment, the tumor will disappear by itself. Why is the same neuroblastoma so different in different children?
In a study published in Nature Cancer, scientists from the German Cancer Research Center (DKFZ) and other institutions challenged this problem. They found that, The loss of an amino acid may explain the disappearance of cancer cells in these children.
This discovery is based on a member of an oncogene family that has attracted much attention recently—— MYCN gene Speaking of. Recently, studies have pointed out that as a regulatory factor in the direction of disease development, MYCN Genes determine whether precursor cells will develop into mature nerve cells or malignant neuroblastoma.
The genome of malignant neuroblastoma contains hundreds of active MYCN The high activity of gene copies leads to the substantial transformation of cancer cell metabolism. But the question is, what benefits does this gene bring to cancer cells? If it can be terminated MYCN Can the process of cancer also be contained?
Based on this idea, the research team MYCN The role of gene in neuroblastoma was studied. They found that, MYCN Highly active neuroblastoma cells have a particularly strong demand for cysteine.
For most cells, cysteine is an important structural unit of protein and lipid. The rapidly proliferating cancer cells obviously need these proteins and lipids to produce new cells.
On the other hand, cancer cells also need cysteine to protect themselves, Remove a large amount of peroxide toxin produced by highly active metabolism. When neuroblastoma cells lack cysteine, they will obtain it through two ways: using the amino acid ingested by the host, or using methionine to produce cysteine through another synthetic path.
The dependence of neuroblastoma cells on cysteine reminds the research team that if cysteine is artificially deprived MYCN In the driven tumor cells, peroxides will begin to accumulate, leading to cell iron death. Therefore, Cysteine may be the Achilles heel of malignant neuroblastoma.
In order to test this conjecture, in the mouse experiment, the research team blocked the intake and synthesis of cysteine, and inactivated a class of enzymes used to consume peroxides. At this time, Due to the large accumulation of peroxides, cancer cells can start the self destruction process through iron death, and the tumor will shrink accordingly.
This study was first confirmed in cancer mice, Iron death can be used to kill highly aggressive neuroblastoma cells.
The same process may explain the spontaneous disappearance of cancer cells in some children with neuroblastoma. "In the first year of life, cells usually acquire less cysteine. Therefore, when these cells start to divide uncontrollably, their cysteine reservoir will be emptied quickly, so iron death will start." Dr. Hamed Alborzinia, the co corresponding author of the paper, explained. some MYCN Inactive neuroblastoma cannot get rid of the result of self clearance, and dies when cysteine deficiency reaches a certain stage.
And for those MYCN For high-risk patients with highly active genes, this study provides a new understanding of the balance of cysteine intake, production and consumption, and also provides more researchers It provides a new idea to start the self destruction process of cancer cells. We expect that through future clinical trials, this process will really be used to treat children with neuroblastoma, so that those unfortunate children can grow up healthily and feel the beauty of the world.
reference material:
[1] Alborzinia， H。， Flórez， A.F。， Kreth， S。 et al。 MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis。 Nat Cancer 3， 471–485 （2022）。 https：//doi.org/10.1038/s43018-022-00355-4
[2] Tumors on withdrawal： Amino acid deficiency shrinks childhood tumors 。 Retrieved Apr 28th， 2022 from https：//www.dkfz.de/en/presse/pressemitteilungen/2022/dkfz-pm-22-27-Tumors-on-withdrawal-Amino-acid-deficiency-shrinks-childhood-tumors.php
This article is from WuXi AppTec content WeChat team
