Physicians decide how to treat brain cancer in part based on what a patient’s tumor looks like under the microscope. But while the microscope can help classify a tumor, it cannot always reveal the molecular changes that drive the disease. And in an era of molecularly targeted therapies, this is what physicians and patients increasingly want to know.
Molecular markers have been identified and even genomic tests have been developed for breast and other common cancers, but progress has been slower in brain cancer. Obtaining the tumor tissue needed for molecular studies is difficult, and hundreds, if not thousands, of samples are needed to capture the genetic diversity of brain cancer.
Nonetheless, there is reason for optimism. Some of the first genomic studies of cancer included surveys of brain tumors, and for the first time, several clinical trials are enrolling patients based on tumor markers, such as combined deletions on chromosomes 1 and 19.
A database being developed by NCI and its partners around the country could also help move the field toward more individualized care. The Glioma Molecular Diagnostic Initiative (GMDI) is collecting and integrating molecular, genetic, and clinical data on hundreds of patients with gliomas, the most common type of brain tumor.
Changing the System
The March 1 issue of Cancer Research includes one of the first publications using the study’s database. The researchers propose a new classification system for gliomas based on tumor gene activity. While the results are considered preliminary, they illustrate the promise of an approach that seeks to integrate different types of information from patients with the disease, the researchers said. “Unlike the standard classification system for gliomas, we came up with a system that is based purely on biology,” said lead investigator Dr. Howard A. Fine, chief of NCI’s Neuro-Oncology Branch in the Center for Cancer Research. “The results confirm and extend the findings of smaller glioma classification studies published previously,” he added. Collectively, these studies show that there are subtypes of brain tumors defined not by their appearance under the microscope, but rather by the molecular pathways that are altered in tumors, said Dr. Mark Gilbert, professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center, who was not involved in the research. “These studies all have the same goal,” Dr. Gilbert continued. “For a hundred years we’ve made treatment decisions on the basis of looking at brain tumor tissue under the microscope. Yet we know that two patients can have very different outcomes even though their tumors look identical, so it would be helpful if we could figure out the pathways that made the cancers different.”
Clinical Genomics
Created to help attain that goal, GMDI has enrolled more than 800 patients with gliomas at 14 institutions around the country. A tumor sample collected during surgery for each patient is sent to NCI for molecular analysis. Clinical information on each patient is then linked to molecular and genetic descriptions of the tumor in a public database called REMBRANDT (Repository of Molecular Brain Neoplasia Data). “We have built the largest cancer clinical genomics database for any tumor type, let alone an uncommon type such as glioma,” said Dr. Fine. In the Cancer Research study, the researchers used 159 gliomas from GMDI to develop an algorithm that assigns gliomas to six subtypes under two groups, glioblastomas and oligodendrogliomas. They validated the algorithm in three additional data sets, totaling nearly 700 gliomas. The results confirm what physicians have always known—that some patients will do better than others for reasons that may not be understood, said Dr. Michael Prados, director of translational research in neuro-oncology at the University of California, San Francisco Comprehensive Cancer Center. He also leads a consortium that provided some of the annotated tumor samples used in the analysis. “If we really want to change the outcomes for patients, then we need therapies that address changes in particular pathways,” added Dr. Prados. “We don’t have those therapies now, so the challenge going forward is: How will we use this information to make a difference in patients therapeutically?”
Exploring the Biology
As a next step, Dr. Fine’s group is characterizing the biology of the tumors to inform the development of new therapies. Until very recently, most patients with brain cancer received the same toxic drugs. But with a growing pipeline of molecularly targeted cancer drugs, physicians can start to evaluate these agents rationally in clinical trials.
Given that the most common subtypes may include only about 10 percent of all tumors, the selection of patients for these trials will be critical. A drug may perform poorly in a trial of unselected patients, and therefore could be discarded, even though it may be very effective for a specific subset of patients. “For prognostic purposes, for drug development, and for the design of future clinical trials, we really need to be able to group brain tumors according to their underlying biology,” said Dr. Fine.
The genome surveys published last year and a recent follow-up report about relatively common mutations in brain tumors have set the stage for more individualized approaches to the disease. And while much more work remains to be done, everyone in the field seems to be moving in the same direction. “Information is power, and these studies are all expanding the knowledge base,” said Dr. Prados. “This will let us develop therapies for patients in a more specific way.” —Edward R. Winstead
Discovering the Secrets of Brain Tumors
Genentech seeks accelerated approval of drug to treat brain cancer
Genentech today said it is seeking federal permission to have its cancer-fighting drug Avastin given accelerated approval to treat people with an aggressive form of brain cancer. The U.S. Food and Drug Administration already has approved Avastin for use in combination with chemotherapy to treat colon and breast cancer. In today's announcement, the South San Francisco biotechnology giant said it is seeking approval to have the drug approved to treat glioblastoma, the most common type of brain tumor.
Excerpt:
Is This Realistic for the Average Person Diagnosed with Brain Cancer
Excerpt From:
The story behind Kennedy's brain surgery
What is known is that a few days after Kennedy learned he had a malignant brain tumor in the left parietal lobe, he invited a group of national experts to discuss his case.
The meeting on May 30 was extraordinary in at least two ways.
One was the ability of a powerful patient — in this case, a scion of a legendary political family and the chairman of the Senate’s health committee — to summon noted consultants to learn about the latest therapy and research findings.
The second was his efficiency in quickly convening more than a dozen experts from at least six academic centers. Some flew to Boston. Others participated by telephone after receiving pertinent test results and other medical records.
Cancer risk from cellphone use is still a matter for study
By Shari Roan, Los Angeles Times Staff Writer
That's because scientists still can't say with certainty that placing a cellphone against the head is completely safe, especially for heavy users and people who began using the devices as children. They point to lingering questions over the potential health effects from the energy emitted by the phones, specifically the long-debated risk of developing brain cancer.
Cancer survivors get help for treatment's side effects
Yesterday I came across a very poignant article in the Chicago Tribune about the debilitating side-effects that hinder the quality of life for brain cancer patients.
From The Article
The field of cancer rehab is just starting to take off, said Paul Barnes,
president and CEO of Navitas Cancer Rehabilitation Centers, billed as the first
company in the nation to focus exclusively on personalized, integrated cancer
rehab services.
I think this is such an important issue when dealing with brain cancer - Long Overdue!
Protein in Common Virus
A protein found in the common human virus cytomegalovirus (CMV) appears to be a key factor in making brain tumors more aggressive and faster spreading (Cancer Research, Feb. 1, 2008).
The researchers, from the California Pacific Medical Center Research Institute in
"IE1 delivers a one-two punch to tumor cells. We detect the CMV IE1 protein in nearly all malignant brain tumors, and we find that it can make tumor cells more aggressive by affecting two major pathways," said Charles Cobbs, MD, the lead author of the study.
"First, it inhibits two key tumor suppressor proteins in the brain tumor cells; then it promotes the most important growth signaling pathway in the tumor itself. By modulating these cellular pathways, this viral protein makes the tumor cells more aggressive."
Dr. Cobbs first made the discovery that CMV was associated with malignant brain tumors in 2002. Now, by identifying the mechanism that helps CMV fuel tumors, the researchers say it could speed up the search for new treatments.
"This opens up the door to the possibility of treating the malignant brain tumors with an antiviral drug, a simple oral medication that could dramatically help patients fight off a previously fatal cancer" says Liliana Soroceanu, PhD, MD, a co-author of the study.
High grade glioma tumors are the most common form of brain cancer. They are difficult to treat because surgical cure is not an option, and radiation and chemotherapy have only limited success against them. As a result the tumors are typically fatal within a year, claiming some 20,000 lives in the
CMV is a common virus, causing a persistent infection in 50 to 80 percent of all Americans. Because it often produces few symptoms most people are unaware they are infected. In normal, healthy individuals CMV poses few risks, but it can pose serious health problems for people with compromised immune systems such as people with HIV/AIDS, organ transplant recipients, and pregnant women and their fetus.
Tears, shock over Edward M Kennedy's brain cancer diagnosis
Washington -
Stunned silence swept Tuesday across the US Congress, observers said.
One colleague wept.
Senator Edward "Ted" Kennedy, left-wing icon and champion of the rights of workers and the poor, had been diagnosed with brain cancer.
The announcement sent shockwaves throughout Washington's political establishment, with Republican and Democratic leaders alike paying tribute to his achievements and significance in US political life.
A grim diagnosis: Kennedy's brain cancer is worst kind
By LAURAN NEERGAARD – 17 hours ago
WASHINGTON (AP) — A malignant glioma — the diagnosis doctors gave Sen. Edward M. Kennedy — is the worst kind of brain cancer. Malignant gliomas strike almost 9,000 Americans a year. Survival statistics are grim — few live three years and for the worst subtype, half die within a year.
Documentary On PBS Tonight: The Truth About Cancer
Tonights 2 hour documentary takes a look at the distance we've come, and have yet to travel, in the messy battle still being waged by patients, their families, and their doctors—decades after President Nixon declared a "war on cancer" in 1971.
Following the program is a frank discussion hosted by breast-cancer survivor Linda Ellerbee with a panel of experts, each of whom has also had cancer. U.S. News's Health Editor Dr. Bernadine Healy participates, sharing her own experiences with brain cancer. "I think all too often people who get the diagnosis of cancer think that they have to fold their tents and go off and get ready to die—that it's a dying time," says Healy. Her take—and the title of her memoir, released last year—it that it's a "living time." The challenge we are faced with now, she says, is to turn cancer into a manageable chronic disease, not only in a medical sense but especially in an emotional one
http://www.usnews.com/blogs/on-medicine/2008/04/15/a-moving-documentary-about-families-and-cancer.html
Targeting Brain Cancer
Click here for a print-friendly version
Reported April 2, 2008 
CLEVELAND
Data-handling technique finds genes to be team players in curbing brain cancer cell growth
| The search for cancer genes is increasingly a matter of molecular “To Tell the Truth,” as scientists seek to distinguish genes actually involved in the disease from those that are imposters. Powerful gene-scanning technology often reveals hundreds or thousands of genetic irregularities in tumor tissue, making it critical for investigators to winnow out the true culprits. |
Excerpt: A Viral Attack against Brain Tumors
A viral view: Researchers at Yale University have genetically engineered a virus (green) that specifically attacks brain tumors in mice (red). The virus kills the primary tumor masses (B) and migrating tumor cells (E), while leaving healthy tissue intact.
Credit: Van den Pol/Yale University
Now researchers at Yale University have found that a virus that's in the same family as rabies effectively kills an aggressive form of human brain cancer in mice. Using time-lapse laser imaging, the team watched vesicular stomatitis virus (VSV) rapidly home in on brain tumors, selectively killing cancerous cells in its path, while leaving healthy tissue intact. What's more, Anthony Van den Pol, lead researcher and professor of neurosurgery and neurobiology at Yale, says that VSV is able to self-replicate and produce secondary lines of defense.
Electromagnetic Resolution for 2008?
by Marcelle Cendrars / December 26th, 2007
Dissident Voice, CA - Dec 26, 2007
Studying brain cancer, for example, is one of the toughest jobs in epidemiology, according to Devra (Let’s provide a cozy sit-down, holiday ambiance here, ..
