The four survival strategies of tumor cells in childhood cancer

June 5, 2018, Lund University
An illustration and summary of the four strategies (free to use for news purposes). Credit: Catrin Jakobsson

Cancer cells in children tend to develop by following four main trajectories—and two of them are linked to relapse of the disease, according to a study led by Lund University in Sweden, now published in Nature Genetics. The four strategies can occur simultaneously in a single tumour.

The researchers mapped out the genomes of from more than 50 tumours in order to identify the four strategies. The genomes of often evolve, both to avoid the body's own defence mechanisms and to survive treatment with chemotherapy or other drugs. When cancer cells multiply, mutations develop, and new types of tumour cells, known as clones, can occur.

A challenge when treating patients is that within a single tumour, there may be several distinct clones, which individually trigger the development of cancer in varying ways. The clones may also respond to chemotherapy differently. More knowledge about how such clones develop is therefore an important part of improving treatment.

"We wanted to learn more about how some tumours evade treatment and the strategies the cancer cells develop," explains Jenny Karlsson at Lund University, one of the researchers behind the study.

The developmental trajectories of tumours have so far been unknown in childhood cancer. Therefore, the researchers mapped out the genomes of cancer cells from more than 50 tumours from patients with Wilms tumour, neuroblastoma and rhabdomyosarcoma. This allowed the researchers to track the types of mutations that caused the emergence of four main survival strategies: tolerance, coexistence, competition and chaos.

"The strategies are key, as they give us an indication of the evolutionary capacity a tumour has at the time of discovery. Patients with the first two variants generally have good outcomes, while the latter two strategies are associated with risk of ," says Professor David Gisselsson Nord, who led the study.

If two of the strategies—competition or chaos—exist in the tumour at the onset of illness, the risk of relapse is more than 50 percent.

"The same two strategies were found when we analysed relapse tumours. It seems that some cancer cells are programmed from the outset to single-handedly create a relapse. Relapsed tumours had genomes that were often radically altered compared to the patient's first tumour. We conclude that the first tumour should not be used as a proxy to predict targeted treatment in case of a relapse. A new biopsy is well warranted. The genome of the tumour usually changes over time," says David Gisselsson Nord.

The next step will be to identify which mechanisms drive the survival strategies adopted by the cancer in the initial phase of the disease.

"If we knew more about how the environment in the patient's tissues triggers cancer cells to develop, we could also influence how they change during treatment and perhaps prevent a relapse. We are now applying for funding to conduct such studies and to evaluate, in a major study, whether the four strategies can really be used in the clinic," concludes David Gisselsson Nord.

The four strategies:

  1. Tolerance. New clones are allowed to emerge locally in the tumour, but they stay in their place of origin. The researchers did not find that this was associated to relapse.
  2. Coexistence. New clones grow together with the original , and coexist with them in many parts of the tumour. The researchers did not find that this strategy was associated to relapse.
  3. Competition. A new clone outcompetes the original tumour cell, and then builds up parts of the tumour entirely on its own. The researchers found that this strategy was associated with increased risk of relapse.
  4. Chaos. New clones mutate intensively so that a variety of cell types emerge in a specific part of the at the same time. This strategy was also associated with increased risk of relapse.

Explore further: Aggressive breast cancer already has resistant tumour cells prior to chemotherapy

More information: Jenny Karlsson et al. Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer, Nature Genetics (2018). DOI: 10.1038/s41588-018-0131-y

Related Stories

Aggressive breast cancer already has resistant tumour cells prior to chemotherapy

April 20, 2018
Difficult to treat and aggressive "triple-negative" breast cancer is chemoresistant even before chemotherapy begins, a new study by researchers from Karolinska Institutet and the University of Texas MD Anderson Cancer Center ...

Anti-inflammatory strategy stops aggressive childhood cancer

May 29, 2018
Researchers at Karolinska Institutet and Karolinska University Hospital have discovered that an anti-inflammatory drug candidate inhibiting the prostaglandin E2 producing enzyme mPGES-1 in the tumour stroma reduces tumour ...

Potential therapy identified for aggressive breast cancer

January 25, 2018
The European Cancer Stem Cell Research Institute, based with Cardiff University, has repurposed a current cancer therapy, TRAIL, to find a new treatment for advanced cancers that are resistant to anti-hormone therapy.

New method for identifying most aggressive childhood cancers

January 28, 2015
A research group at Lund University in Sweden has found a new way to identify the most malignant tumours in children. The method involves studying genetic 'micro-variation', rather than the presence of individual mutations.

New study reveals late spread of breast cancer and backs key role of early diagnosis

August 14, 2017
Breast cancer cells that spread to other parts of the body break off and leave the primary tumour at late stages of disease development, scientists from the Wellcome Trust Sanger Institute and their collaborators have found.

Tumor-trained T cells go on patrol

May 15, 2017
'Tumour-trained' immune cells - which have the potential to kill cancer cells - have been seen moving from one tumour to another for the first time. The new findings, which were uncovered by scientists at Australia's Garvan ...

Recommended for you

Biologists discover how pancreatic tumors lead to weight loss

June 20, 2018
Patients with pancreatic cancer usually experience significant weight loss, which can begin very early in the disease. A new study from MIT and Dana-Farber Cancer Institute offers insight into how this happens, and suggests ...

Researchers find 11 genes responsible for the spread of cancer

June 20, 2018
A groundbreaking discovery by University of Alberta researchers has identified previously-unknown therapeutic targets that could be key to preventing the spread of cancer.

'Kiss of death' cancer: How computational geeks may have uncovered a therapy for a deadly disease

June 19, 2018
It's called the 'kiss of death'. Triple negative breast cancer has no targeted drug therapy and, as such, the only hope for these patients is chemotherapy. Triple negative breast cancer is aggressive and deadly. Patients ...

Ovarian cancer cells switched off by 'unusual' mechanism

June 19, 2018
Scientists at the Ovarian Cancer Action Research Centre at Imperial College London have discovered a mechanism that deactivates ovarian cancer cells.

Team discovers gene mutations linked to pancreatic cancer

June 19, 2018
Six genes contain mutations that may be passed down in families, substantially increasing a person's risk for pancreatic cancer. That's according to Mayo Clinic research published in the June 19 edition of the JAMA. However, ...

Breast cancer could be prevented by targeting epigenetic proteins, study suggests

June 19, 2018
Researchers at the Princess Margaret Cancer Centre in Toronto have discovered that epigenetic proteins promote the proliferation of mammary gland stem cells in response to the sex hormone progesterone. The study, which will ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.