New drug targets for childhood cancer neuroblastoma identified

Date:
February 5, 2021
Source:
Wellcome Trust Sanger Institute
Summary:
The largest single cell study to date of the childhood cancer,
neuroblastoma, has discovered that all neuroblastomas arise from
a single type of embryonic cell called sympathoblasts.



FULL STORY ==========================================================================
The largest single cell study to date of the childhood cancer,
neuroblastoma, has answered important questions about the genesis of the disease. The researchers from the Wellcome Sanger Institute, Great Ormond Street Hospital (GOSH) and the Princess Ma'xima Center for Pediatric
Oncology, discovered that all neuroblastomas arise from a single type
of embryonic cell called sympathoblasts.


==========================================================================
The study, published today (5 February 2021) in Science Advances, sought
to understand why neuroblastomas range in severity, with some easy to
treat and others having relatively low five-year survival rates. The
fact that all neuroblastomas arise from sympathoblasts makes them an
attractive drug target, because these cells exist only in the tumour
after the child is born.

Neuroblastoma is a rare cancer that generally affects children under five
years old. It begins in the abdomen, usually in the adrenal glands --
hormone- producing glands above the kidneys. Neuroblastoma is remarkable
in that its severity can vary greatly between individuals. In some
children the cancer will disappear without treatment, whereas in others
the cancer is relentless. The five-year survival rate for neuroblastoma
is one of the lowest of all childhood cancers*.

This varied outlook prompted the researchers to ask whether the range of severity could be caused by neuroblastomas arising from different cell
types at different stages of the child's development in the womb. This
was made possible by the advent of single cell mRNA sequencing,
a high-resolution technology that can identify different cell types
present in a tissue according to the genes expressed by individual cells.

In this study, gene expression of 19,723 cancer cells was analysed and
compared to a reference of 57,972 developmental adrenal cells in the
hope of identifying the cell types from which neuroblastomas arise and
to find novel treatment targets.

Dr Jan Molenaar, a senior author of the study from the Princess
Ma'xima Center for Pediatric Oncology in the Netherlands, said:
"What is most striking about our findings is that despite the great
diversity of clinical behaviour of neuroblastoma, there is an overarching neuroblastoma cell type that is found in all patients. The identification
of sympathoblasts as the root of all neuroblastoma is an important step
towards understanding how the disease develops and, hopefully, how we
can treat it." Currently, many cancer treatments cause serious side
effects for the patient.

But in recent years, technological advances have sped up drug development
by allowing researchers to identify differences between the biological processes, such as the expression of a particular gene, within healthy
human cells and those within cancerous ones. These differences can
be exploited to attack cancer cells without affecting the patient's
healthy cells.

The presence of sympathoblasts, a developmental cell type not normally
found in children after they are born, makes it a promising drug target
for the treatment of neuroblastoma.

Dr Karin Straathof, a senior author of the study from Great Ormond
Street Hospital, said: "Neuroblastoma is an unusual cancer in that some
tumours resolve without intervention, yet the disease still has one of
the lowest five- year survival rates of any childhood cancer. This study
fills important gaps in our knowledge of what neuroblastoma cells are
and revealed novel treatment targets. My hope is that new, less intrusive therapies can be developed by targeting sympathoblasts, a developmental
cell type that exists only in neuroblastoma tumours after a child is
born." As well as facilitating the discovery of sympathoblasts as the
root of neuroblastoma, the single-cell reference map of the developmental adrenal gland will also contribute to the Human Cell Atlas project**. The project aims to create comprehensive reference maps of all types of human
cells -- the fundamental units of life -- as a basis for understanding
human health and diagnosing, monitoring, and treating disease.

Dr Sam Behjati, a senior author of the study from the Wellcome Sanger
Institute and Cambridge University Hospitals, said: "Our study shows
the power of looking at individual childhood cancer cells in revealing
not just one, but a plethora of novel treatment ideas. This raises the
exciting prospect that a single cell atlas of all types of paediatric
tumours may transform our understanding of childhood cancer."

========================================================================== Story Source: Materials provided by Wellcome_Trust_Sanger_Institute. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Gerda Kildisiute, Waleed M. Kholosy, Matthew D. Young et al. Tumor
to
normal single-cell mRNA comparisons reveal a pan-neuroblastoma
cancer cell. Science Advances, 2021 DOI: 10.1126/sciadv.abd3311 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/02/210205150145.htm

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