Key to Treating Cancer May Be Finding its Original Cell

August 11, 2008,

(PhysOrg.com) -- Cancer biologists are turning their attention to the normal cells that give rise to cancers, to learn more about how tumor growth might be stopped at the earliest opportunity.

"Identifying the specific, normal cells that cancers come from can provide critical insight into how cancers develop," said Robert Wechsler-Reya, an associate professor of Pharmacology and Cancer Biology at Duke University Medical Center. "This may help us develop more rational and effective approaches to treatment."

Every cancer comes from a normal cell. The hard part is finding the cell at the root of each particular subtype of cancer. For the first time, the Duke team has identified two types of cells in the brain that can give rise to the malignant brain tumor medulloblastoma. This dangerous cancer, which occurs most commonly in children, is currently treated with a combination of surgery, chemotherapy and radiation, which have extremely severe side effects, said Wechsler-Reya, who is a member of the Preston Robert Tisch Brain Tumor Center at Duke.

To find the normal cells at the root of medulloblastoma, Wechsler-Reya's laboratory, in collaboration with Brandon Wainwright's laboratory at the University of Queensland in Australia, created mouse models of medulloblastoma by turning off the patched gene, a key regulator of cell growth in the developing brain cerebellum. In particular, they tested the effects of shutting off patched in granule neuron precursors (GNPs), which can only make one particular type of nerve cell (neuron), or in stem cells, which can make all the different cell types in the cerebellum.

When they deleted patched in the neuron precursors, 100 percent of the mice developed medulloblastoma. Deleting patched from stem cells initially led to the formation of many more stem cells. However, most of these stem cells went on to form normal cell types within the cerebellum. Only the patched-less stem cells that gave rise to GNPs went on to form medulloblastoma tumors.

According to Wechsler-Reya, these studies provide the first definitive proof that medulloblastoma can be triggered in a granule neuron precursor or a stem cell. But even more importantly, they suggest that when it comes to cancer formation, the cell type in which a mutation happens is as important as the mutation itself. Although stem cells that lack patched also gave rise to other forms of brain cells, those cells did not form the tumors.

"Simply mutating a gene is not enough to cause cancer," Wechsler-Reya said. "The mutation has to happen in the right cell type at the right time. In the case of patched, GNPs provide the critical context for tumor formation."

Wechsler-Reya said that cancer biologists need to learn more about the genes that regulate proliferation (cell division), differentiation, survival, and programmed cell death in normal cells. A mutation in a proliferation gene, for example, can send the cell on a path of exaggerated division of cells -- becoming a fast-growing tumor. Understanding the way these genes are controlled during normal development can shed light on how they go awry in human cancers.

This work, published in the August issue of Cancer Cell, was funded by the Hope Street Kids Foundation, the Kislak-Sussman Fund, the Children's Brain Tumor Foundation, the Pediatric Brain Tumor Foundation, the McDonnell Foundation, and a grant from the National Institute of Neurological Disorders and Stroke. The collaborative work in Dr. Wainwright's lab was supported by the National Health and Medical Research Council of Australia, the ARC Special Research Centre for Functional and Applied Genomics, the Queensland Cancer Fund.

Provided by Duke University

Explore further: Researchers identify a protein that keeps metastatic breast cancer cells dormant

Related Stories

Researchers identify a protein that keeps metastatic breast cancer cells dormant

January 23, 2018
A study headed by ICREA researcher Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona) has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light ...

Cancer tumours could help unravel the mystery of the Cambrian explosion

January 23, 2018
Could tumours help us explain the explosion of life of Earth? Scientists have typically explained the period of history when large animal species became much more diverse very quickly as the result of the planet's rising ...

Study: Cells of three advanced cancers die with drug-like compounds that reverse chemo failure

January 23, 2018
Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggressive cancers—ovarian, prostate and breast.

Scientists find mechanisms to avoid telomere instability found in cancer and aging cells

January 23, 2018
Researchers from Instituto de Medicina Molecular (iMM) João Lobo Antunes have found that a functional component of telomeres called TERRA has to be kept constantly in check to prevent telomeric and chromosomal instability, ...

Scientists block the siren call of two aggressive cancers

January 23, 2018
Aggressive cancers like glioblastoma and metastatic breast cancer have in common a siren call that beckons the bone marrow to send along whatever the tumors need to survive and thrive.

New approach attacks 'undruggable' cancers from the outside in

January 23, 2018
Cancer researchers have made great strides in developing targeted therapies that treat the specific genetic mutations underlying a patient's cancer. However, many of the most common cancer-causing genes are so central to ...

Recommended for you

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

Workouts may boost life span after breast cancer

January 22, 2018
(HealthDay)—Longer survival after breast cancer may be as simple as staying fit, new research shows.

Cancer patients who tell their life story find more peace, less depression

January 22, 2018
Fifteen years ago, University of Wisconsin–Madison researcher Meg Wise began interviewing cancer patients nearing the end of life about how they were living with their diagnosis. She was surprised to find that many asked ...

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

E_L_Earnhardt
not rated yet Aug 12, 2008
Accelerated mitosis is the "hall-mark" for any and ALL cancers. This is electronically triggered
as is "normal rate mitosis". The rate of cell division is governed by electron "speed & spin", which is read as "heat" or electrical charge. COOL or "discharge" the cell to change rate!

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.