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Characterization of neuroblastoma chemotherapy resistance

Adamič, Dora (2024) MOBN03 20232
Degree Projects in Molecular Biology
Popular Abstract
Mechanisms of chemotherapy resistance in childhood cancer

Cancer is a group of diseases in which cells start to divide uncontrollably, until they start to invade other tissues. Neuroblastoma is the third most common early childhood cancer. It develops in the sympathetic nervous system, and it is most often found in the adrenal gland. High-risk neuroblastoma is challenging to treat and has poor prognosis.

Treatment of patients with Neuroblastoma involves chemotherapy, called the COJEC protocol, followed by surgery and other treatments. However, treatment resistance is a major problem, and it needs to be studied further to find better therapies for resistant neuroblastoma.

Recent findings have shown that neuroblastoma tumors are... (More)
Mechanisms of chemotherapy resistance in childhood cancer

Cancer is a group of diseases in which cells start to divide uncontrollably, until they start to invade other tissues. Neuroblastoma is the third most common early childhood cancer. It develops in the sympathetic nervous system, and it is most often found in the adrenal gland. High-risk neuroblastoma is challenging to treat and has poor prognosis.

Treatment of patients with Neuroblastoma involves chemotherapy, called the COJEC protocol, followed by surgery and other treatments. However, treatment resistance is a major problem, and it needs to be studied further to find better therapies for resistant neuroblastoma.

Recent findings have shown that neuroblastoma tumors are made of different cells, or different cell phenotypes, which have distinct responses to therapy. The first type of cells is referred to as the adrenergic phenotype, while the latter is called mesenchymal phenotype, which has previously been associated with treatment resistance.

My project focused on the mechanisms behind neuroblastoma chemotherapy resistance. We worked with patient material, grown in mice. We treated mice with neuroblastoma with COJEC, which reduced the tumor but in the end it grew back. The relapsed tumor was reimplanted in new mice and treated with COJEC again which influenced the tumors in various fashions: some shrank, some kept growing but slower, and some were resistant to treatment and grew equally fast.

Why do tumors of same origin respond to treatment differently?
Relapsed tumors sparked our interest because of their varied responses to treatment, despite being exposed to the same conditions. Therefore, we investigated the differences between the tumors, using advanced techniques, such as RNA analysis and staining with antibodies, specific to neuroblastoma cells, or specifically adrenergic and mesenchymal cells.

Although the detailed RNA and protein analysis did not allow us to point to specific genes responsible for treatment resistance, our data suggested that treatment resistant tumors had a higher amount of the mesenchymal phenotype. When we compared that to neuroblastoma cells, grown in the laboratory, we saw that the relapsed cells also had higher levels of the mesenchymal phenotype in comparison to untreated cells. Therefore, our results suggest that mesenchymal phenotype could play an important role in chemoresistance in NB and could thus be a valuable therapeutic target. To prove that, we treated the mesenchymal cell state with a drug, which remarkably lowered cells’ ability to multiply. Overall, our results provided us with insight to the mechanisms of chemotherapy resistance and identified a novel therapeutic approach towards relapsed and chemotherapy resistant neuroblastoma.

Master’s Degree Project in Molecular Biology, Medical Biology, 60 credits 2024
Department of Biology, Lund University

Advisors: Daniel Bexell, associate professor, senior lecturer and Aleksandra Adamska, PhD Molecular Pediatric Oncology, Translational Cancer Research, Lund University (Less)
Please use this url to cite or link to this publication:
author
Adamič, Dora
supervisor
organization
course
MOBN03 20232
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9176093
date added to LUP
2024-10-04 11:15:57
date last changed
2024-10-04 11:15:57
@misc{9176093,
  author       = {{Adamič, Dora}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Characterization of neuroblastoma chemotherapy resistance}},
  year         = {{2024}},
}