Vaishnavi Kardale, Bioinformatics Centre, Savitribai Phule Pune University
Our cells divide for growth. Cancer starts when the growth of the cells gets out of control. Any cell can become cancerous at any stage and any age. Cancer development can begin even in fetal cells.
What is Neuroblastoma?
Neuroblastoma (NB) is a type of cancer that starts in a very early form of nerve cells that are commonly found in embryos or fetuses. Neuro refers to nerves and blastoma refers to cancer that occurs in premature cells. This cancer occurs most commonly in infants and young children. Neuroblastoma occurs in the nerve cells of the sympathetic nervous system. In our body, all the functions are controlled by the nervous system. Some functions are voluntary while some are involuntary. Involuntary functions are the ones that are not in our control like breathing, digestion, heart rate, and other functions. These functions are included in the autonomic nervous system. The sympathetic nervous system is a part of the autonomic nervous system.
Neuroblastoma begins in the abdomen and is commonly found on adrenal glands on top of the kidneys. NB accounts for 15% of all pediatric cancer. The survival of high-risk neuroblastoma is less than 50%. Approximately half of the high-risk patients do not respond to the current prescribed therapy protocol or relapse in the first two years of the treatment. In addition to these many patients develop multiple drug resistance and severe drug toxicities. NB is complex and exhibits heterogeneity in biological, morphological, clinical, and genetic features making it difficult to develop therapies against it. This has made NB a topic of interest for a lot of researchers.
How far has research come?
Genomic analysis suggests that chromosome instability (mis-segregation of the chromosome during cell division) might be responsible for the development of NB. It is crucial to understand the defects in spindle formation and centromere separation that are leading to chromosome instability. One of the observations by researchers is that high-risk NB patients had a hemizygous deletion of chromosome 11q 22-23. This is peculiar as genes on chromosome 11 have a role in DNA repair and its loss may be associated with the progression of NB.
Amongst all therapy options immunotherapy has emerged as the most effective one yet as it causes less toxicity among patients than other patients. With rapid modifications to the treatment, it is expected that the side effects are going to reduce.
Very few compounds that target epigenetic factors are under clinical trial at the moment. More research needs to be done on them. New approaches should also be developed while improvising the older ones. One of the new approaches in the development of HIFU (High-Intensity Focused Ultrasound). MR (Magnetic Resonance)-HIFU is being developed for the treatment of NB. It is being implemented in relapsed NB patients. Phase I trials are currently in progress at Children’s National Research Institute in Washington DC. Combining MR-HIFU with existing chemotherapy needs to be implemented to augment chemo-response of NB, increase local control, and decrease toxicity.
What next?
Currently, research is being done using mice, zebrafish, and chick chorioallantoic membrane (CAM). Using more physiologically relevant models could have a high impact on research as it can mimic the genetic complexity of the tumour. A patient-derived xenograft model or 3D tissue-engineered system is recommended to better understand the pathogenesis of NB.
Overall, it is crucial to understand the genetic complexity of NB and the molecular pathways it follows for the progression and onset of cancer. The findings in this area should be exploited to develop new targets for therapy. The purpose of developing new treatments should be to cure children with NB with minimal toxicity and side effects.
Also read: Understanding Cancer pathophysiology via isotopic tracing
Reference:
- Zafar, A., Wang, W., Liu, G., Wang, X., Xian, W., McKeon, F., Foster, J., Zhou, J., & Zhang, R. (2021). Molecular targeting therapies for neuroblastoma: Progress and challenges. Medicinal Research Reviews, 41(2), 961–1021. https://doi.org/10.1002/med.21750
Author info:
Vaishnavi Kardale is a master’s student at the Bioinformatics Centre, Savitribai Phule University. She is interested in protein folding mechanisms and wants to study them further.
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