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New insights into childhood cancer

Mechanisms of tumor growth and regression

Date:
December 10, 2018
Source:
Charité - Universitätsmedizin Berlin
Summary:
Peripheral nervous system tumors, known as neuroblastoma, are one of the most common types of childhood tumors. Researchers have now studied the genetic factors behind different tumor subtypes and their prognoses. Their findings enable clinicians to predict the precise clinical course of the disease, and to adapt their treatment regimens accordingly.
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Peripheral nervous system tumors are one of the most common types of childhood tumors. While some of these tumors, known as neuroblastoma, disappear on their own without treatment, others will continue to grow even despite intensive treatment. As part of an international research endeavor, researchers from Charité -- Universitätsmedizin Berlin have studied the genetic factors behind different tumor subtypes and their prognoses. Their findings enable clinicians to predict the precise clinical course of the disease, and to adapt their treatment regimens accordingly. The study has been published in the journal Science.

One of the article's last-named authors, Prof. Dr. Johannes Schulte, of Charité's Department of Pediatrics, Division of Oncology and Hematology, sums up the study's main findings as follows: "The data produced by our work provide us with a precise means of classifying different neuroblastoma phenotypes." Working alongside pediatric oncologists from University Hospital Cologne, in addition to various other colleagues, Prof. Schulte succeeded in deciphering the genetic code of neuroblastoma cells. The researchers identified mutations in the RAS and p53 cancer signal transduction pathways -- changes that are often associated with a poor prognosis. However, the researchers also found some cases of spontaneous tumor regression in patients with these mutations. It was only by merging the genetic data on these cancer signal transduction pathways with information on the mechanisms responsible for maintaining the length of telomeres (structures found at ends of our chromosomes) that the researchers gained a better understanding of the mechanisms involved in producing different neuroblastoma subtypes. This in turn enabled them to make precise predictions regarding disease prognosis.

Telomeres are known to act as a 'molecular clock' in human cells. In most of the body's cells, telomeres will shorten each time the cell divides. Once a critical length is reached, the cell receives the signal to stop dividing, resulting in cell growth arrest or cell death. Stem cells and most cancer cells, however, have telomere maintenance mechanisms which ensure that telomere length remains at above the critical length, thus effectively rendering the cell immortal.

The researchers discovered that neuroblastoma tumors only exhibit aggressive growth if these maintenance mechanisms are present. Prognosis was found to be particularly poor in patients with additional mutations affecting the above-mentioned cancer signaling pathways. Given that current treatments are ineffective in the majority of these patients, the ultimate aim is to develop personalized treatments instead of applying unspecific therapies with severe side effects that will not help the patient. Interestingly, in patients without telomere maintenance mechanisms, mutations of the cancer signaling pathways were found to have no bearing on prognosis. Many of these patients show spontaneous tumor regression even without treatment, while others have such a good treatment response that reduced regimens with less side effects may soon become feasible.

"Our study shows that the activation of telomere maintenance mechanisms plays a crucial role in the development of malignant tumors," says Prof. Schulte. The researchers' findings also provide an opportunity to explore and develop new treatment approaches. Targeted treatments that aim to block cancer signaling pathways and telomere maintenance mechanisms constitute one such promising new avenue.


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Materials provided by Charité - Universitätsmedizin Berlin. Note: Content may be edited for style and length.


Journal Reference:

  1. Sandra Ackermann, Maria Cartolano, Barbara Hero, Anne Welte, Yvonne Kahlert, Andrea Roderwieser, Christoph Bartenhagen, Esther Walter, Judith Gecht, Laura Kerschke, Ruth Volland, Roopika Menon, Johannes M. Heuckmann, Moritz Gartlgruber, Sabine Hartlieb, Kai-Oliver Henrich, Konstantin Okonechnikov, Janine Altmüller, Peter Nürnberg, Steve Lefever, Bram de Wilde, Frederik Sand, Fakhera Ikram, Carolina Rosswog, Janina Fischer, Jessica Theissen, Falk Hertwig, Aatur D. Singhi, Thorsten Simon, Wenzel Vogel, Sven Perner, Barbara Krug, Matthias Schmidt, Sven Rahmann, Viktor Achter, Ulrich Lang, Christian Vokuhl, Monika Ortmann, Reinhard Büttner, Angelika Eggert, Frank Speleman, Roderick J. O’Sullivan, Roman K. Thomas, Frank Berthold, Jo Vandesompele, Alexander Schramm, Frank Westermann, Johannes H. Schulte, Martin Peifer, Matthias Fischer. A mechanistic classification of clinical phenotypes in neuroblastoma. Science, 2018; 362 (6419): 1165 DOI: 10.1126/science.aat6768

Cite This Page:

Charité - Universitätsmedizin Berlin. "New insights into childhood cancer." ScienceDaily. ScienceDaily, 10 December 2018. <www.sciencedaily.com/releases/2018/12/181210101915.htm>.
Charité - Universitätsmedizin Berlin. (2018, December 10). New insights into childhood cancer. ScienceDaily. Retrieved May 23, 2024 from www.sciencedaily.com/releases/2018/12/181210101915.htm
Charité - Universitätsmedizin Berlin. "New insights into childhood cancer." ScienceDaily. www.sciencedaily.com/releases/2018/12/181210101915.htm (accessed May 23, 2024).

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