Metabolic State of Brain Cancer Stem Cells Significantly Different than the Cancer Cells They Create

The metabolic state of glioma stem cells, which give rise to deadly glioblastomas, is significantly different from that of the brain cancer cells to which they give birth, a factor which helps those stem cells avoid treatment and cause recurrence later.

Researchers with the UCLA Department of Radiation Oncology at UCLA’s Jonsson Comprehensive Cancer Center also found for the first time that these glioma stem cells can change their metabolic state at will, from glycolysis, which uses glucose, to oxidative phosphorylation, which uses oxygen.

The glioma stem cells’ ability to change their metabolic state at will also allow these stem cells that seed new cancer growth to evade treatment and remain alive, said Dr. Frank Pajonk, an associate professor of radiation oncology and senior author of the study.

“We found these cancer stem cells are substantially different in their metabolic states than the differentiated cancer cells they create, and since they act differently, they can’t be killed in the same way,” Pajonk said. “And as yet, we don’t have anything to target these glioma stem cells specifically.”

The study is published this week in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.

Cancer cells take up large amounts of glucose, which fuels their grow and spread, and allows them to be differentiated from normal cells under Positron Emission Tomography (PET) scanning, which captures metabolic activity. Pajonk and his team found that the glioma stem cells took up much less glucose, which makes them difficult to detect with PET.

Targeting cancer metabolic pathways as a treatment has gained new interest in recent years. However, these cancer stem cells that take up less glucose could evade those treatments by utilizing glucose more efficiently through oxidative phosphorylation, which would not be targeted by such drugs.

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Driver of breast cancer stem cell metastasis

Living Well Beyond Breast Cancer: A Survivor's Guide for When Treatment Ends and the Rest of Your Life Begins

Researchers at the University of Michigan Comprehensive Cancer Center have found that a cancer gene linked to aggressive spread of the disease promotes breast cancer stem cells. The finding implies a new way to target the behavior of these lethal cells.

The finding involves the cancer gene RhoC, which has previously been shown to promote metastasis of many types of cancer. RhoC levels increase as breast cancer progresses and high levels of RhoC are associated with worse patient survival.

Cancer stem cells are the small number of cells within a tumor that are believed to fuel the tumor’s growth and spread. Researchers believe traditional chemotherapy and radiation treatments often become ineffective because they do not kill the cancer stem cells, and that the key to future treatments is to develop drugs that target and kill these cells.

This new study, which appears online in PLoS ONE, suggests a new way to get at the cancer stem cells.

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New drug combo can destroy root of breast cancer cells

Making a breakthrough in the battle against breast cancer, scientists have used a combination of drugs to target cancer stem cells that cause the disease to spread.

Current treatments kill only the surface cells in a breast tumour, but scientists now say they can destroy the root, the Mirror reported.

They hope that the findings, revealed ahead of World Cancer Day, can be used to help women with advanced and aggressive cancers. Targeting cancer stem cells takes us a step closer to better clinical options for those with the disease, said Dr Rob Clarke, of Manchester University.

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Professor donates stem cells to help brother fight cancer

Many of us remain close to our siblings in adulthood, seeing each other through life’s ups and downs. But for Dr. Don Hicks, director of The Center for Church Relations and Church Health at Liberty Baptist Theological Seminary, and his brother Billy, the relationship couldn’t be closer – they share the same blood and the same immune system. That’s because Don donated his stem cells to his brother last year after discovering he was Billy’s only chance at surviving leukemia.

Billy, who lives in Nashville, Tenn., with his wife and three children (two in high school and one in college), had battled the cancer for five years, but the side effects from medications that were helping to keep it in check were too severe. In January 2011, he was given one year to live without a stem cell transplant, the only known cure for the cancer.

After Don underwent eight months of tests and physical exams to determine if he was the perfect match, including three trips to Nashville, Tenn., his stem cells were harvested through his blood (a more preferred method to bone marrow transplants in the past) and the procedure took place in August 2011.

“He did this because he loves me very much. We’ve always been close, and he would do anything for me,” Billy said.

The decision did not come without some risk – the brothers knew there was a chance Don’s stem cells would attack Billy’s body (called “graft-versus-host disease”) and lead to serious health issues or death.

“It was hard for me to deal with the fact that my stem cells could kill him or cure him,” Don wrote in an update to family and friends before the transplant. “Billy helped me by saying, ‘I have no other choice. I am willing to receive your stem cells and trust God.’ Joking, he said, ‘I will not have you arrested for your stem cells killing me!’”

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One Compound Detects and Treats Malignant Tumors and Certain Cancer Stem Cells

Madison, Wisconsin – More than a decade of laboratory research at the University of Wisconsin has proven that a single chemical compound may both detect and treat malignant tumors and certain cancer stem cells.
In three posters presented at the annual meeting of the American Association for Cancer Research (AACR) in Chicago, March 31-April 4, UW-Madison researchers describe exciting advances involving CLR1404, described as a “diapeutic” agent that can both image and destroy a wide range of malignant tumors and the one type of cancer stem cells examined so far.

The presentations are based on basic research in the lab of Dr. Jamey Weichert, associate professor of radiology at the UW School of Medicine and Public Health (SMPH) and a member of the UW Carbone Cancer Center (CCC).
Clinicians at the UW School of Medicine and Public Health and elsewhere are interested in assessing CLR1404′s potential. Several clinical trials evaluating both the cancer imaging and therapeutic capabilities of CLR1404 are under way at the Carbone Cancer Center, with more scheduled to begin soon.

Dr. John Kuo, director of the Comprehensive Brain Tumor Program at UW Hospital and Clinics and a cancer stem-cell scientist at the School of Medicine and Public Health, is studying the possibility of using CLR1404 to treat glioblastoma multiforme (GBM), a deadly form of brain cancer, by targeting GBM stem cells.
In one of the American Association for Cancer Research posters (#3495), Kuo and Weichert describe how CLR1404 decreases glioblastoma stem cell activity, suppresses GBM growth and improves animal survival.

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