Still in the womb: what affects the birth of a baby with a tumor?

Neuroblastoma is the most common cancer in infants and the third most common malignant tumor in children after leukemia and brain tumors. These tumors originating from neural crest cells can occur anywhere in the sympathetic nervous system, with multiple tumor sites and clinical manifestations. 60% of neuroblastomas metastasize. Therefore, it is very important to understand the causes of the development of neuroblastomas and to know exactly how the tumor “orders” to begin to metastasize.

Neuroblastoma is considered a malignant tumor of middle and late embryonic development, so it has been taken as a model for a fundamental study of the developmental patterns of childhood cancers that occur even in childhood, according to Igor Adameyko, a representative of the NCMU international collaboration. Uterine. Neuroblastoma, one of the types of embryonic tumors, is seen in 99% of cases in children under 15 years of age.

“Any cancer cell is like normal cells, but at some point they suddenly start growing and the body dies,” explains Igor Adameyko. – So far, no idea what exactly is driving this growth.

In our study, for the first time, we answer the question of what are the genetic programs that trigger the activity of genes in healthy cells and facilitate the transition to diseased cells.

For the study, the scientists took embryos at an advanced stage from week 6 to week 12 of fetal development. This is clinical material from Swedish hospitals. Isolated cells were examined (of fundamental importance) to understand the potential activity of each. Such work was needed to characterize human embryonic development at the level of individual cells that consistently implement their genetic programs.

“Imagine you have a keyboard with which you can play different melodies,” explains Igor Adameyko. – It’s a genome. It is the same in all cells, but for some reason we have completely different cells as a result of development: skin, heart, liver, etc. This is because on this keyboard, different melodies can be played, for example, which should sound at a certain time of the day.

And suddenly you have a crazy character (cancer cell) that starts playing them at the wrong time and confuses them. And if you understand how this cell “makes its own music,” then you can influence it.

Neuroblastoma remains an “understudied” malignant tumor as it cannot be studied in a mouse model due to differences in mouse and human embryonic development.

“Neuroblastomas do not occur naturally in mice, and current genetic models cannot reproduce the full spectrum of natural features of the disease,” the authors write in a paper published in the journal Nature Genetics, which summarizes the achievements of the NCMU scientists.

As a result of the study, three genetic programs were identified that cause the transition of healthy cells to malignant cells. These three transitions can potentially occur in the tumor, helping it to avoid chemotherapy because of its higher plasticity.

“In the case of neuroblastoma, we found three transitions between the three cell types,” says Adameyko. – It is important to understand that malignant tumors are heterogeneous, in their structure there are several types of cells that hardly interact with each other. Also, they can cross each other. Often, some cells are dominant and chemotherapy is directed at them. And the rest continue to settle, circulate in the body, form metastases.

Thanks to the work of scientists, it has now become clear how exactly these transitions occur and under what conditions they are possible. This will help keep the tumor under control, preventing it from metastasizing, which will allow you to live with neuroblastomas for many years in the future.

“Neuroblastomas usually begin to develop in the adrenal glands, these are paired endocrine glands located above the top of the human kidneys,” says NCMU director Pavel Volchkov. — Since the disease has an endocrine nature, it is actively studied at the Endocrinological Research Center of the Ministry of Health of the Russian Federation, where our National Endocrine Diseases Personalized Medicine Center was opened. We try to combine the basic research that Igor Adameyko is engaged in with applied research. This work is important for understanding the causes of neuroblastomas, which will enable us to increase the survival rates of such patients in the near future.”

“Today, personalized medicine allows you to very quickly move from basic discoveries to the use of new technologies at the patient’s bedside,” Professor Marina Sekacheva, Director of the Institute of Personalized Oncology at Sechenov University, told socialbites.ca.

– This fundamental work, deservedly recognized worldwide, as published in one of the best scientific journals in the world, allows us to study embryogenesis, to understand the processes that occur in the earliest stages of laying human organs. and systems. In the future, it will be possible to influence the found mechanisms of tumor growth that will make it possible to treat neuroblastoma with great success, and possibly even with the aid of gene therapy.”