John McCain and Glioblastoma

US Senator John McCain recently had removal of an aggressive brain tumor known as glioblastoma multiform. It is a highly aggressive form of cancer that often returns quickly to the same spot, even with surgery, radiation therapy, and chemotherapy. McCain;s tumor was associated with a small blood clot above the Arizona Republican’s left eye, and surgeons removed it using a minimally invasive procedure. A statement from the senator’s office explains that imaging suggests that the neurosurgeon successfully removed the abnormality, at least the gross, measurable tumor.

What is Glioblastoma?

A brain tumor is a mass of abnormal cells that originated in the brain itself. GMB arises from supportive tissue (not the nerves themselves) in the brain (glial cells). Rarely, glioblastoma runs in families, but most individuals with GBM have no family history of the disease. While cancer can spread to the brain from other organs such as the lungs, GBM begins in the brain and only uncommonly spreads outside of it. For most individuals, we do not know the cause of GBM, but exposure to radiation to the brain is a known risk factor for the future development of cancer of the brain.

Next steps?

Following a recovery period of 3 to 4 weeks, patients typically proceed to radiation therapy (RT). The RT targets the tumor (or where it use to be) and often the surrounding edema (water) plus an inch or so. Often, those with GBM also have an oral chemotherapy known as temozolamide at the same time as radiation therapy (and sometimes after it). This approach of fractionated (for example, Monday through Friday for 6 weeks) radiotherapy plus oral chemotherapy is a category 1 recommendation of the National Comprehensive Cancer Network, a group of some of the top cancer treatment facilities in America. For those over 70, one may consider this approach versus a shortened course of radiation therapy versus chemotherapy with deferred radiation therapy.

In 2011, the Food and Drug Administration approached a portable medical device that generates low-intensity electric fields termed Tumor Treating Fields (TTF) for GBM. The use of this device (placed on the head) may yield results similar to chemotherapy, but with lower toxicity and improved quality of life.

Prognosis

Half of patients will survive beyond about 18 months. While 10 year survival is quite uncommon, it is possible. We need better treatments, and clinical trials are an important part of achieving this. I’m Dr. Michael Hunter.

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The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minutes. Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

 

Brain Tumors: New Hope?

What You Need to Know: Targeted therapies are a growing and groundbreaking field in cancer care in which drugs or other substances are designed to interfere with genes or molecules that control the growth and survival of cancer cells. Now, scientists have identified a novel interaction between a microRNA and a gene that could lead to new therapies for the most common and deadly form of brain tumor, malignant glioma.

Background: Scientists at Virginia Commonwealth University (USA) have identified a novel interaction between a microRNA and a gene that could lead to new therapies for the most common and deadly form of brain tumor, malignant glioma.

Details, details: Investigators provided the first evidence of an important link between a specific microRNA, miR-184, and a cancer promoting gene, SND1, in the regulation of malignant glioma. miR-184 is known to suppress tumor development by regulating a variety of genes involved in cancer growth, while SND1 has been shown to play a significant role in the development of breast, colon, prostate and liver cancers. Through a variety of preclinical experiments, the team demonstrated that increasing the expression of miR-184 slows the growth and invasive characteristics of glioma cells through direct regulation of SND1. Additionally, they showed that reduced levels of SND1 led to reduced levels of STAT3, a gene that has been shown to promote the most lethal characteristics of brain cancer.

“Patients suffering from brain tumors are in desperate need of improved therapies,” says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine and director of the VIMM. “We’re hopeful that this new understanding of the relationship between miR-184 and SND1 ultimately will lead to the development of new drugs that reduce SND1 expression and improve patient outcomes.”

Prior studies have shown that levels of miR-184 are unusually low in tissue samples from patients with malignant gliomas. Using advanced computer analysis techniques designed to study and process biological data, the researchers identified SND1 among a handful of other genes that miR-184 helps regulate. Knowing SND1 is implicated in a variety of cancers and having previously defined its role in liver cancer, Emdad, Fisher and their colleagues explored this relationship further. They confirmed low levels of miR-184 expression in human glioma tissue samples and cultured cell lines as well as an increase in the expression of SND1 compared to normal brain tissue. Using data from a large public brain tumor database called REMBRANDT, the researchers confirmed that patients with lower levels of SND1 survived longer than those with elevated SND1 expression.

“We still have a long way to go and many challenges to overcome before we will have therapies that are ready for clinical use, but this is a significant first step in the process,” says Emdad, member of the Cancer Molecular Genetics research program at Massey, assistant professor in the VCU Department of Human and Molecular Genetics and member of the VIMM. “Future studies will aim to explore the relationship between SND1 and STAT3, identify additional microRNAs that may be relevant to malignant glioma and explore the effects of drugs that block SND1 expression in more advanced preclinical models.”

I’m Dr. Michael Hunter.

Journal Reference:
L. Emdad, A. Janjic, M. A. Alzubi, B. Hu, P. K. Santhekadur, M. E. Menezes, X.-N. Shen, S. K. Das, D. Sarkar, P. B. Fisher. Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness. Neuro-Oncology, 2014; DOI: 10.1093/neuonc/nou220

Virginia Commonwealth University. “Important gene interaction defined that drives aggressive brain cancer.” ScienceDaily. ScienceDaily, 11 December 2014. <www.sciencedaily.com/releases/2014/12/141211162501.htm>.

Different Brain Tumors Have the Same Origin

What You Need to Know: Glioma is a common name for serious brain tumors. Different types of glioma are usually diagnosed as separate diseases and have been considered to arise from different cell types in the brain. Now researchers at Uppsala University, together with American colleagues, have shown that one and the same cell of origin can give rise to different types of glioma. This is important for the basic understanding of how these tumors are formed and can contribute to the development of more efficient and specific glioma therapies.

The most common primary, malignant brain tumors in adults, called glioma, are formed from cells in the brain that are not nerve cells. These are serious tumors that lack highly effective treatment, and relapses are common. There are different types of glioma, classified according to an established system based on which cell type the tumor arises from. The most common gliomas are astrocytoma, which have their name from astrocytes, and oligodendroglioma, which are believed to arise from oligodendrocytes. Patients with astrocytoma have a poorer prognosis than oligodendroglioma patients, and the two tumor types are considered separate clinical diagnoses.

“Since the tumor types look different and have different prognoses it has been assumed that they arise from different cells of origin in the brain, but the fact is that the exact cell of origin has not been determined for any glioma. We have for a long time been interested in finding out more about the origin of gliomas and how it is associated with the genetic alterations that cause the tumor,” says lead researcher Lene Uhrbom.

In collaboration with colleagues in the United States, Uhrbom’s research group has studied glioma development in mice. Using tumor models for both astrocytoma and oligodendroglioma, which are very similar to human tumors, they showed that one and the same cell type, called oligodendrocyte precursor cells, could give rise to both tumor forms.

The researchers discovered that it is not the cell of origin but rather the genetic aberrations that control which tumor type is formed. By analysing gene activity in a large number of human astrocytoma and oligodendroglioma they could also conclude that the tumors are more similar to one another than was previously believed. This supports their finding that the glioma diagnoses can have the same origin.

“We saw that the same kind of more differentiated cell of origin, which has previously only been shown to give rise to oligodendroglioma, also can give rise to astrocytoma. New findings such as these increase our understanding of the basic mechanisms that cause glioma,” says Lene Uhrbom.

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Uppsala University. “Different brain tumors have the same origin, new findings show.” ScienceDaily. ScienceDaily, 28 October 2014. <www.sciencedaily.com/releases/2014/10/141028214055.htm>.

Breast Cancer Spreads to brain By Disguising Itself as Brain Cells

Often, several years can pass between the time a breast cancer patient successfully goes into remission and a related brain tumor develops. During that time, the breast cancer cells somehow hide, escaping detection as they grow and develop.

Breast cancer cells disguise themselves as neurons, becoming “cellular chameleons,” found the scientists from City of Hope in Duarte, California. This allows them to slip undetected into the brain and then develop into tumors. The discovery is being heralded as “a tremendous advance in breast cancer research.”

Although breast cancer is a very curable disease—with more than 95% of women with early-stage disease surviving after 5 years—breast cancer that metastasizes to the brain is difficult to fight. Only about 20% of patients survive 1 year after diagnosis.

“There remains a paucity of public awareness about cancer’s relentless endgame,” said Rahul Jandial, MD, PhD, a City of Hope neurosurgeon who headed the breast-cancer-and-brain-tumor study, published in the Proceedings of the National Academy of Sciences (2014; doi:10.1073/pnas.1322098111). “Cancer kills by spreading. In fact, 90% of all cancer mortality is from metastasis,” Jandial said. “The most dreaded location for cancer to spread is the brain. As we have become better at keeping cancer at bay with drugs such as herceptin, women are fortunately living longer. In this hard-fought life extension, brain metastases are being unmasked as the next battleground for extending the lives of women with breast cancer.”

He added, “I have personally seen my neurosurgery clinic undergo a sharp rise in women with brain metastases years—and even decades—after their initial diagnosis.”

Jandial and other scientists wanted to explore how breast cancer cells cross the blood-brain barrier—a separation of the blood circulating in the body from fluid in the brain—without being destroyed by the immune system.

The researchers’ hypothesis was that,  given that the brain is rich in many brain-specific types of chemicals and proteins, perhaps breast cancer cells that could exploit these resources by assuming similar properties would be the most likely to flourish. These cancer cells could deceive the immune system by blending in with the neurons, neurotransmitters, other types of proteins, cells, and chemicals.

Taking samples from brain tumors resulting from breast cancer, the scientists found that the breast cancer cells were exploiting the brain’s most abundant chemical as a fuel source. This chemical, gamma-aminobutyric acid (GABA), is a neurotransmitter used for communication between neurons.

When compared with cells from nonmetastatic breast cancer, the metastasized cells expressed a receptor for GABA, as well as for a protein that draws the transmitter into cells. This allowed the cancer cells to essentially masquerade as neurons.

“Breast cancer cells can be cellular chameleons (or masquerade as neurons) and spread to the brain,” Jandial said.

He added that further study is required to better understand the mechanisms that allow the cancer cells to achieve this disguise, and he hopes that, ultimately, unmasking these disguised invaders will result in new therapies.

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