A recent study conducted by a team of researchers from the Hopp Children’s Cancer Center Heidelberg (KiTZ), the German Cancer Research Center (DKFZ), and Heidelberg University Hospital (UKHD) has shed light on the cellular characteristics of certain brain tumors in children, which play a significant role in determining tumor aggressiveness. The research, published in the journal Nature Communications, analyzed individual cells to gain insights into the genetic programs they possess and their developmental pathways within the tumor.
Medulloblastoma, the most common malignant brain tumor in children, presents unique challenges due to its location in the cerebellum and its potential to damage vital brain centers. The tumor can exhibit diverse characteristics and outcomes based on tissue and genetic criteria, leading to the classification of different risk groups. While some subtypes of medulloblastoma progress aggressively with metastases, others can be effectively treated through a combination of surgery, chemotherapy, and radiotherapy.
The team of researchers utilized a novel method to investigate the factors influencing the benign or malignant nature of tumors at the cellular level. They focused on a specific type of medulloblastoma called medulloblastoma with extensive nodularity (MBEN), which is characterized by the presence of small tissue chambers connected in a grape-like manner within the tumor.
The findings of the study revealed that tumor cells located in these nodules were no longer actively dividing and exhibited genetic programs similar to mature brain cells. However, the intermediate areas of the tumor contained various cell types, including immune and connective tissue cells, as well as aggressive tumor cells that continued to divide uncontrollably. These aggressive cells possessed genetic programs resembling those of fast-growing medulloblastomas and immature nerve cells.
Interestingly, as the aggressive tumor cells migrated into the nodules, they matured back into nerve-like cells and ceased dividing. This maturation process explained the relatively favorable course of MBEN tumors compared to other types of medulloblastoma. According to Kristian Pajtler, a pediatric oncologist involved in the study, certain childhood tumors experience a blockage in the normal development process, causing cancer cells to resemble immature precursor cells that remain active in division due to specific genetic programs.
The research team dissected the tumors of nine young MBEN patients into individual cellular components and analyzed the genetic programs of each cell. Through a bioinformatic method developed in collaboration with Karsten Rippe’s team at DKFZ, they were able to determine the precise location of these cells within the tumor. This method proved to be crucial for medulloblastoma research, allowing the team to understand the distinctions among different areas within the tumor and the characteristics of individual cell types.
Blocking the maturation process is a potential therapeutic strategy being explored to prevent malignant progression in children and redirect cancer cells towards a benign direction. Pajtler suggested that MBEN tumors may require a slight nudge in this direction. Although most children with MBEN tumors can be successfully treated through surgery and additional therapies, these treatments can be intensive and may result in severe long-term side effects for young patients.
The findings of this study offer significant insights into brain tumors in children and highlight the importance of understanding cellular characteristics in determining tumor behavior. Further research into therapeutic interventions targeting the maturation process may lead to improved treatment options with reduced long-term side effects for young patients.
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1. Source: Coherent Market Insights, Public sources, Desk research
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