Learn About Brain Cancer

Brain Cancer

A disease of the brain in which cancer cells (malignant) arise in the brain tissue. Cancer cells grow to form a mass of cancer tissue (tumor) that interferes with brain functions such as muscle control, sensation, memory, and other normal body functions.

Brain Tumor

An abnormal growth of tissue in the brain.  Unlike other tumors, brain tumors spread by local extension and rarely metastasize (spread) outside the brain.

Clinical Trials

Research studies done to determine whether new drugs, treatments, or vaccines are safe and effective.  They are conducted in three phases:

  • Phase I
    In this phase, small groups of people are treated with a certain dose of a new agent that has been extensively studied in the laboratory. During the trial, the dose is increased group by group to find the highest dose that does not cause harmful side effects. Usually there is no control treatment for comparison. This process determines a safe, appropriate dose for use in Phase II.
  • Phase II
    This phase provides continued safety testing of a new agent, along with an evaluation of how well it works against a specific type of cancer. The new agent is given to groups of people and is usually compared with a standard treatment.
  • Phase III
    This phase answers research questions across the disease continuum and includes large numbers of participants so that the differences in effectiveness of the new agent can be evaluated. If the results of this phase merit further use of the new agent, the pharmaceutical company will usually submit a New Drug Application to the FDA.

Diagnostics

The determination of the nature of a disease or ailment.  A clinical diagnosis is based on the medical history and physical examination of the patient.

Glial Cells

Cells that provide structure to the central nervous system and insulate and protect neurons (cells that transmit electrical impulses that allow seeing/hearing/smelling/tasting).

Glioma

The term used to refer to the most prevalent primary brain tumors.  Gliomas arise from glial tissue, which supports and nourishes cells that send messages from the brain to other parts of the body.

Glioblastoma

Also known as glioblastoma multiforme, this is the most common and aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52 percent of all functional tissue brain tumor cases and 20 percent of all intracranial tumors.

GBM

GBM is an abbreviation for glioblastoma multiforme.

Translational Genomics

Innovative advances arising from the Human Genome Project, applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases

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Scientists Use a New Strategy for Brain Cancer Treatment

Brain-penetrating particle attacks deadly tumors

Jul 02, 2013 by Eric Gershon

Brain-penetrating particle attacks deadly tumors

(Phys.org) —Scientists have developed a new approach for treating a deadly brain cancer that strikes 15,000 in the United States annually and for which there is no effective long-term therapy. The researchers, from Yale and Johns Hopkins, have shown that the approach extends the lives of laboratory animals and are preparing to seek government approval for a human clinical trial.

“We wanted to make a system that would penetrate into the brain and deliver drugs to a greater volume of tissue,” said Mark Saltzman, a biomedical engineer at Yale and principal investigator of the research. “Drugs have to get to tumor cells in order to work, and they have to be the right drugs.”

Results were published July 1 in the Proceedings of the National Academy of Sciences.

Glioblastoma multiforme is a malignant cancer originating in the brain. Median survival with standard care—surgery plus chemotherapy plus radiation—is just over a year, and the five-year survival rate is less than 10 percent.

Current methods of drug delivery have serious limitations. Oral and intravenously injected drugs have difficulty accessing the brain because of a biological defense known as the blood-brain barrier. Drugs released directly in the brain through implants can’t reach migrating tumor cells. And commonly used drugs fail to kill the cells primarily responsible for tumor development, allowing regrowth.

The researchers developed a new, ultra-small drug-delivery particle that more nimbly navigates brain tissue than do existing options. They also identified and tested an existing FDA-approved drug—a fungicide called dithiazanine iodide (DI)—and found that it can kill the most aggressive tumor-causing cells.

“This approach addresses limitations of other forms of therapy by delivering drugs directly to the area most needed, obviating systemic side-effects, and permitting the drug to reside for weeks,” said neurosurgeon Dr. Joseph M. Piepmeier, a member of the research team. Piepmeier leads clinical research for Yale Cancer Center’s brain tumor program.

The drug-loaded nanoparticles are administered in fluid directly to the brain through a catheter, bypassing the blood-brain barrier. The particles’ tiny size—their diameter is about 70 nanometers—facilitates movement within brain tissue. They release their drug load gradually, offering sustained treatment.

In tests on laboratory rats with human brain cancers, DI-loaded nanoparticles significantly increased median survival to 280 days, researchers report. Maximum median survival time for rats treated with other therapies was 180 days, and with no treatment, survival was 147 days. Tests on pigs established that the new drug-particle combination also diffuses deep into brains of large animals.

The nanoparticles are made of polymers, or strings of repeating molecules. Their size, ability to control release, and means of application help them permeate brain tissues.

Researchers screened more than 2,000 FDA-approved drugs in the hunt for candidates that would kill the cells most responsible for human tumor development, brain cancer stem cells. Overall, DI worked best.

The scientists believe the particles can be adapted to deliver other drugs and to treat other central nervous system diseases, they said.

Read more at: http://phys.org/news/2013-07-brain-penetrating-particle-deadly-tumors.html#jCp

A Promising New Cancer Drug

Promising New Cancer Drugs Empower the Body’s Own Defense System

“If you look five years out, most of this meeting will be about immunotherapy,” said Dr. Mario Sznol.
SCOTT MORGAN / ASCO
By ANDREW POLLACK
June 3, 2013

CHICAGO — The early success of a new class of cancer drugs, revealed in test results released here over the last several days, has raised hope among the world’s top cancer specialists that they may be on the verge of an important milestone in the fight against the disease.

The excitement has spread to Wall Street. Shares of Merck and Bristol-Myers Squibb, which are developing such drugs, rose more than 3 percent on Monday after data from their studies was presented over the weekend at the meeting of the American Society of Clinical Oncology.

The drugs, still generally in early testing, work in an entirely new way, by unleashing the immune system to attack cancer cells much as it attacks bacteria. That could be an alternative to often-debilitating chemotherapy.

Finding ways to use the body’s own defenses has been a goal since the late 1800s, when a New York surgeon named William B. Coley noticed that cancer disappeared in a patient who had a severe bacterial infection.

He then began injecting bacteria into cancer patients to rev up their immune systems. His claims of success were disputed and most attempts since then to harness the immune system have not worked.

The new drugs work by disabling a brake on the immune system called the programmed death 1 receptor, or PD-1. And although the data presented at the meeting was from the earliest stage of testing only, the drugs were the center of attention here, with some doctors predicting that cancer treatment was about to shift.

“If you look five years out, most of this meeting will be about immunotherapy,” said Dr. Mario Sznol, a professor of medical oncology at Yale.

Analysts, who predict billions of dollars in sales, are trying to determine which of the three front-runners — Merck, Bristol-Myers and Roche — have the best drug and how soon the drugs could reach the market. Some think it could be as early as a year and a half from now.

“I think all of you recognize this is a very special moment in oncology,” Dr. Roger M. Perlmutter, head of research and development at Merck, told analysts Sunday at a standing-room-only meeting.

Harnessing the immune system is appealing for several reasons. It might be applicable to many different types of cancer. It might produce longer lasting remissions than can be achieved by chemotherapy or the newer targeted drugs. And it seems somehow more natural and holistic.

“It seems the right thing to do to stimulate our body’s defense rather than take some kind of poison,” said Therese Bocklage, a cancer patient and pathologist from Albuquerque.

Dr. Bocklage thought she had bruised her leg moving a Christmas tree in late 2011. It turned out to be the return of the melanoma she thought had been successfully eradicated by surgery 20 years earlier.

She has been taking Merck’s experimental PD-1 inhibitor, lambrolizumab, as part of a clinical trial since January 2012, and her tumors have disappeared. “If I had had this turn up not last year but six years ago, most likely I’d be dead,” she said.

But there are reasons to be cautious. This is cancer, after all. Many other hoped-for miracles have failed to materialize. This is a conference that has hailed drugs that extend lives by only a few weeks as breakthroughs.

“We’re so used to failure, we get excited very easily,” said Dr. Kim Margolin, an expert on melanoma and immune therapies at the Seattle Cancer Care Alliance.

Most of what is known about the PD-1 drugs is that they shrink tumors significantly in 15 to 50 percent of patients. It is still not clearly established, though there are some hints, that the drugs will let people live longer.

And results seen in trials, under idealized conditions, do not translate perfectly to the real world. One poster presented here looked at use in Britain of Yervoy, a melanoma drug approved in 2011 that disables a different immune system brake. Median survival has been only about half of what was seen in clinical trials.

Moreover, just because the immune system is involved does not make something safe. Ask anyone with lupus, multiple sclerosis or other diseases caused by an aberrant immune system.

Yervoy, made by Bristol-Myers, has some serious side effects caused by overstimulation of the immune system. The newer PD-1 drugs seem remarkably well tolerated so far, though lung inflammation is seen in some patients.

For the last decade or so, the emphasis in oncology has been so-called targeted therapy, in which drugs counteract particular genetic mutations that drive tumor growth. These were supposed to displace conventional chemotherapy, which tends to poison fast-growing cells, both cancerous and healthy ones, causing serious side effects.

Targeted therapy has had some great successes, particularly the leukemia drug Gleevec. But cancer cells, which tend to mutate rapidly, can develop resistance to the targeted therapies. And it is becoming more difficult to develop drugs for each narrow population of patients with a particular tumor mutation.

The PD-1 drugs are in a sense a return to a one-size-fits-all approach. And it might be harder for the tumor to become resistant to the immune system, which can adapt, than to a single drug.

In fact, what most excited researchers here this weekend was “the tail.” When researchers plot on a graph how many patients remain alive over time, the curves tend to drop to near zero for metastatic cancer. A successful drug slows the rate of decline, but eventually almost all patients die from the cancer.

But with Yervoy and, experts hope, with the PD-1 drugs, there appears to be fraction of patients who do not die of the disease, at least for a long time. The curve levels out in a plateau.

Dr. Sznol said that of five patients treated at Yale with the Bristol-Myers PD-1 blocker, nivolumab, two had no evidence of recurrence even two years after stopping the drug.

Over all, 133 melanoma patients at various clinics took nivolumab in the Phase 1 trial. Median survival was 16.8 months, with 62 percent of patients alive at one year and 43 percent alive after two years. There was no comparison group in the study, but with the existing melanoma drugs, about 24 to 33 percent of patients are alive after two years, Dr. Sznol said.

So if the immune system is so effective, why doesn’t it cure cancer on its own? One reason is that cancerous cells are the body’s own cells, though mutated, and might not be recognized by the immune system as foreign. Another is that the tumors act to suppress the immune system.

Much of the previous attempts at cancer immunotherapy have focused on the first problem — trying to train the immune system to recognize the tumor and attack it.

The PD-1 drugs tackle the second problem of immune system suppression. How many cancers this will work for is still unclear. Much of the early work has been in melanoma, which is known to be more susceptible than many other tumors to immune system attack. There are cases, though rare, in which the immune system vanquishes melanoma on its own.

What is encouraging doctors is that the drugs can shrink some lung cancer tumors, which have not been considered particularly susceptible to immune attack. There are sporadic reports of cases with other cancers as well, like colorectal cancer.

http://mobile.nytimes.com/2013/06/04/health/promising-new-cancer-drugs-empower-the-bodys-own-defense-system.html

Former NFL Coach Loses Battle To Brain Cancer

Chuck Fairbanks, ex-New England Patriots coach, 79

By Associated Press

OKLAHOMA CITY — Chuck Fairbanks, who spent six seasons as coach of the New England Patriots and coached Heisman Trophy winner Steve Owens at Oklahoma, died Tuesday in Arizona after battling brain cancer. He was 79. Oklahoma said in a news release that Fairbanks died in the Phoenix suburb of Scottsdale.

Colorado hired Fairbanks away from the Patriots, but he was just 7-26 in three seasons, including an 82-42 loss at home to the Sooners and his replacement, Barry Switzer. He won 46 games for New England, a franchise record at the time. The Patriots made the playoffs in their fourth season under Fairbanks in 1976 and two years later were on their way to their first outright AFC East title when owner Billy Sullivan angrily suspended him for the final regular-season game because he had agreed to go to Colorado. Fairbanks returned for the playoffs, but New England lost to Houston. He was 0-2 in the playoffs with New England.

Fairbanks left the Buffs to become coach and general manager of the New Jersey Generals of the USFL. He was fired after one season.

Fairbanks was 52-15-1 in six years with the Sooners, including an Orange Bowl victory his first season and consecutive Sugar Bowls wins in 1971-72 before taking over the Patriots.

The Sooners went 10-1 and beat Tennessee in the Orange Bowl in Fairbanks’ first year in 1967. He won 11 games each of last two seasons with OU, beating Auburn and Penn State in the Sugar Bowl.

“His squads won three Big Eight championships and helped lay the foundation for the program’s ongoing success with the installation of the wishbone-T offense,” current Oklahoma coach Bob Stoops said in a statement.

Fairbanks worked in real estate and golf-course development after his coaching career. He occasionally worked as a consultant for NFL teams in training camp, including with the Dallas Cowboys when Bill Parcells was coach.

 

http://www.nfl.com/news/story/0ap1000000156947/article/chuck-fairbanks-exnew-england-patriots-coach-79

A Virtual Brain

Bringing a Virtual Brain to Life

By TIM REQUARTH

For months, Henry Markram and his team had been feeding data into a supercomputer, four vending-machine-size black boxes whirring quietly in the basement of the Swiss Federal Institute of Technology in Lausanne.

The Blue Brain computer has 10,000 virtual neurons. The colors represent the neurons’ electric voltage at a specific moment.

The boxes housed thousands of microchips, each programmed to act like a brain cell. Cables carried signals from microchip to microchip, just as cells do in a real brain.

In 2006, Dr. Markram flipped the switch. Blue Brain, a tangled web of nearly 10,000 virtual neurons, crackled to life. As millions of signals raced along the cables, electrical activity resembling real brain waves emerged.

“That was an incredible moment,” he said, comparing the simulation to what goes on in real brain tissue. “It didn’t match perfectly, but it was pretty good. As a biologist, I was amazed.”

Deciding then that simulating the entire brain on a supercomputer would be possible within his lifetime, Dr. Markram, now 50, set out to prove it.

That is no small feat. The brain contains nearly 100 billion neurons organized into networks with 100 trillion total connections, all firing split-second spikes of voltage in a broth of complex biological molecules in constant flux.

In 2009, Dr. Markram conceived of the Human Brain Project, a sprawling and controversial initiative of more than 150 institutions around the world that he hopes will bring scientists together to realize his dream.

In January, the European Union raised the stakes by awarding the project a 10-year grant of up to $1.3 billion — an unheard-of sum in neuroscience.

“A meticulous virtual copy of the human brain,” Dr. Markram wrote in Scientific American, “would enable basic research on brain cells and circuits or computer-based drug trials.”

An equally ambitious “big brain” idea is in the works in the United States: The Obama administration is expected to propose its own project, with up to $3 billion allocated over a decade to develop technologies to track the electrical activity of every neuron in the brain.

But just as many obstacles stand in the way of the American project, a number of scientists have expressed serious reservations about Dr. Markram’s project.

Some say we don’t know enough about the brain to simulate it on a supercomputer. And even if we did, these critics ask, what would be the value of building such a complicated “virtual brain”?

Henry Markram traces his fascination with the brain to a school assignment in his native South Africa. He was 14, and as he sat in the library reading about depression, he was astonished to discover there might be “molecular explanations to mental illness” that could be treated with drugs.

That set him on a path to medical school, where he planned to become a psychiatrist. But as a medical student, he realized that we know next to nothing about what prescription drugs really do to the brain.

To understand mental illness, he reasoned, we need to understand the brain first. “So I dropped out of medical school,” he said, “and got on a plane to do some real neuroscience.”

He went to the Weizmann Institute of Science in Israel to earn a Ph.D., followed by a stint at the National Institutes of Health in the United States on a Fulbright scholarship. That work led to a position with the Nobel Prize-winning neurophysiologist Bert Sakmann at the Max Planck Institute in Germany.

At Dr. Sakmann’s lab, Dr. Markram made his most famous discovery.

He was pondering how the brain learns cause and effect. He set up an experiment to record the electrical activity from two connected neurons in a slice from a rat’s brain, and discovered that the neurons required a precise sequence of voltage spikes to change the strength of their connections. He speculated that the mechanism might be at the root of our notion of causality.

That work has now been cited thousands of times. Yet as Dr. Markram’s reputation grew, so did his impatience.

Neurons are organized into interconnected circuits that can number in the millions. Dr. Markram realized that to make real progress linking neurons to behavior, experimenting on two neurons at a time “just wasn’t enough.”

In his first faculty position, at the Weizmann Institute, he set up a wildly ambitious new experimental rig that could record data not just from 2 neurons in a rat’s brain but also from 12.

“His rig made NASA look tame,” recalled Dr. Markram’s postdoctoral adviser at the N.I.H., Elise F. Stanley, who visited him at the Weizmann in 1995. “There was so much equipment that you couldn’t even see the brain tissue.”

Soon Dr. Markram would learn that his son, Kai, had autism. “You know how powerless you feel,” he said. “You have this child with autism, and you, even as a neuroscientist, really don’t know what to do.”

He began to question the impact of his work. “I realized that I could write a high-profile research paper every year, but then what?” he said. “I die, and there’s going to be a column on my grave with a list of beautiful papers.”

Dr. Markram decided he needed to change his approach. Experiments, he realized, were not enough.

After hearing of a new I.B.M. supercomputer, he asked himself, What if each microchip of the supercomputer represented a neuron in the brain? You could run simulations to perform virtual experiments and, unlike in real experiments, watch every single “neuron” in action. “If I build in enough biological detail,” he reasoned, “it would behave like a real brain.”

Dr. Markram moved his lab to the Swiss Federal Institute of Technology, which agreed to buy the $10 million supercomputer. Armed with data from 20,000 experiments, Dr. Markram began to build Blue Brain.

By 2008, he said, his team had created a “digital facsimile” of a cylindrical piece of tissue in the rat cortex. In 2011, the team announced it had simulated a “virtual slice” of brain tissue with one million neurons.

He proposed the Human Brain Project, which would scale up Blue Brain to simulate the human brain. Dr. Markram would not be able to do it alone, so he appealed to the broader scientific community for support.

But many scientists are highly skeptical of Blue Brain’s accomplishments.

While the team may have achieved a computer simulation of something, critics say, it was not a brain slice.

“It was completely meaningless, just random activity,” said Alexandre Pouget, a neuroscientist at the University of Geneva, referring to the stunning visualizations that Dr. Markram’s group presents at conferences. “The claim that he simulated a rat’s cortex is completely ridiculous.”

And in a time of increasing competition for research grants, some scientists worry that the Human Brain Project will make funds even scarcer. “There could be indirect effects,” acknowledged Andrew Houghton, a deputy at the European Commission.

But concerns run even deeper.

Some researchers say it is premature to invest money in a simulation while important principles of brain function remain to be discovered.

“We’re probably in the time of Galileo in biology,” said Christof Koch, of the Allen Institute for Brain Science in Seattle. “Darwin, Crick and Watson have given us the equivalent of Galileo and Newton, but there isn’t any equivalent to Einstein’s theory of relativity.”

Other critics say the project is too open-ended — that it makes little sense without clearly defined criteria for success.

“It’s not like the Human Genome Project, where you just have to read out a few billion base pairs and you’re done,” said Peter Dayan, a neuroscientist at University College London. “For the human brain, what would you need to know to build a simulation? That’s a huge research question, and it has to do with what’s important to know about the brain.”

And Haim Sompolinsky, a neuroscientist at the Hebrew University of Jerusalem, said: “The rhetoric is that in a decade they will be able to reverse-engineer the human brain in computers. This is fantasy. Nothing will come close to it in a decade.”

Some say the controversy surrounding Dr. Markram’s work distracts from the real issue: How should neuroscience harness its resources to achieve true understanding of the brain?

“Some 10,000 laboratories worldwide are pursuing distinct questions about the brain,” Dr. Koch of the Allen Institute wrote in the journal Nature. “Neuroscience is a splintered field.”

Dr. Markram agreed. The Human Brain Project, he said, will provide a “unifying principle” for scientists to rally around.

For the first time, data from laboratories around the world will be in one place, he said, adding that trying to build a simulation will drive advances in fields like computing and robotics. An entire division of the project is devoted to creating a new breed of intelligent robots with “neuromorphic” microchips designed like neurons in the human brain.

“The biggest success for me,” Dr. Markram said, “would be if after 10 years we have a new model for neuroscience, where everyone works together. It’s about a new foundation.

“Putting the problem on the horizon is very important,” he continued. “When people say, ‘Well, the brain is so complicated that our grandchildren will solve it,’ we put it over the horizon.”

http://www.nytimes.com/2013/03/19/science/bringing-a-virtual-brain-to-life.html?pagewanted=all&_r=0

Harnessing the Power of Fluorescent Light

Fluorescent Tracer ‘Lights Up’ Brain Tumor for Surgery

A bright pink glow showed the precise pathway a glioma took to spread through the brain

By Barbara Bronson Gray
HealthDay Reporter

TUESDAY, Feb. 19 (HealthDay News) — Neurosurgeons report that they harnessed the power of fluorescent light to illuminate a brain tumor so the entire growth could be removed.

A report describes a case in which a patient with glioblastoma swallowed a pill, called 5-ALA, and was taken to surgery about four hours later. The medication attached itself to tumor cells, causing them to glow brightly. Once the skull was opened, the doctors focused a blue light on the tumor, which gave the cancerous cells a pink glow, so the surgeons could differentiate malignant tissue from healthy tissue.

“This is a very, very good thing,” said study author Mitchel Berger, chairman of neurosurgery at the University of California, San Francisco. “In this case, we just happened to notice we could see evidence of the tumor spreading along the way of the ventricles [a communicating network of brain cavities], which showed we could see tumor dissemination.”

The authors noted that the best way to extend survival is to remove as much of the brain tumor as possible. The research is published in the Feb. 19 issue of the Journal of Neurosurgery.

It’s not always easy to see precisely where a tumor has spread in the brain. Some types of tumors can be particularly difficult to identify and remove, even with the benefit of MRI and surgical microscopes.

The use of fluorescence appears to be more effective than MRI technology, at least in this case, because the glow allows surgeons to see microscopic remnants of the tumor and areas of the cancer that might be mistaken for edema, or swelling, Berger explained. “This is an inexpensive way to identify high-grade tumors,” he said.

Glioblastomas are a fast-growing type of tumor that usually occurs in adults and affects the brain more often than the spinal cord, according to the U.S. National Cancer Institute.

Why do tumor cells respond differently to the fluorescent drug than the body’s other cells do? Their metabolism involves porphyrin, which has a tremendous ability to absorb light, Berger explained. Porphyrin is an organic compound, like the pigment in red blood cells. The pill used in the case report is derived from porphyrin.

The report focused on the case of a 56-year-old man who had undergone resection of a glioblastoma located in the right occipital lobe of his brain in 2005. Several years later, when symptoms reappeared, an MRI scan showed three distinct, new sites of tumor in the patient’s right temporal lobe.

In surgery, when the surgeons viewed the fluorescent tumor cells, they could tell rather than being a new tumor, the cancer had spread from its original location on the right side of the brain through a pathway along the wall of the right ventricle. The researchers found that the use of 5-ALA during surgery enabled them to see the actual pathway of the tumor as it had spread.

The use of 5-ALA changed the patient’s prognosis. “Multi-centric disease worsens the prognosis,” Berger explained.

While the technique has been used in Europe for several years, the U.S. Food and Drug Administration has not approved the use of 5-ALA in the United States. Any surgeons using 5-ALA do so with limited permission from the FDA, Berger noted. The medication, 5-ALA, is manufactured by DUSA Pharmaceuticals.

Dr. Michael Schulder, vice chairman of the department of neurosurgery at North Shore University Hospital in Manhasset, N.Y., explained that “while the FDA considers 5-ALA a drug, which would require a lengthy process for approval, neurosurgeons see it as a surgical aid, which would take far less time to get the OK.”

While Schulder said he thinks 5-ALA probably will add about six months to the anticipated survival of patients with high-grade gliomas, he said that attempts to improve the ability to remove these tumors will only go so far. “In the end, however helpful the use of 5-ALA or similar compounds may be in the surgical removal of brain cancers, it won’t be the answer. The treatments will have to be biological to truly have an impact on survival, and ultimately, on a cure.”

Schulder said he thinks it would be possible for fluorescence to be used in other types of surgeries, if surgeons could become comfortable using a surgical microscope with the benefit of a special light (something neurosurgeons are accustomed to using). He noted that he also thinks the technique might apply to some spinal surgeries, where visualizing the spinal cord is critical.

 

http://health.usnews.com/health-news/news/articles/2013/02/19/fluorescent-tracer-lights-up-brain-tumor-for-surgery

Understanding Brain Tumors

Unraveling the Causes of Brain Tumors

There are many types of brain tumors. Unfortunately, the cause behind most of these tumors remains a mystery.

Medically reviewed by Pat F. Bass III, MD, MPH
While an estimated 359,000 people in the United States have aspinal cord or brain tumor, doctors do not yet know much about what causes these tumors. This fact, although disappointing, is understandable considering the remarkable range of differences among these tumors in adults and children.

There are more than 120 different types of spinal cord and brain tumors. These tumors, also called central nervous system (CNS) tumors, are sometimes benign (non-cancerous) and sometimes cancerous.

In addition, some tumor types occur more often in children than in adults. And adult tumors are not the same as children’s tumors.

Brain Tumor: Risk Factors

Certain factors have been found to increase a person’s risk for a spinal cord or brain tumor. These include:

  • Being a Caucasian male
  • Being older than 70
  • Being younger than age 8
  • Having a family history of brain tumors
  • Being exposed to radiation
  • Being exposed to certain chemicals

But just because a person may be at risk for a brain tumor, doesn’t mean they will get one. What these factors tell us is that people who get a brain tumor often fall into the above categories.

Brain Tumor: Genetic Disorders

While researchers do not know much about what causes brain and spinal cord tumors, they do know that some genetic disorders cause brain tumors. But fewer than 5 percent of brain tumors result from these genetic disorders, including neurofibromatosis, a condition in which nerve tissues grow tumors.

That leaves 95 percent of all brain tumors whose cause is not yet known. But research is under way to better understand what causes brain and spinal cord tumors.

Brain Tumor: The Cancer Genome Atlas

“The most exciting new initiative is the Cancer Genome Atlas,” says Andrew Sloan, MD, director of the Brain Tumor and Neuro-Oncology Center at University Hospitals Case Medical Center in Cleveland. The Cancer Genome Atlas Research Network is a collaborative effort funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute of the National Institutes of Health.

The network, whose goal is to discover more about the molecular basis of cancer, recently published the first results of a major, comprehensive study of glioblastoma. Glioblastomas account for 23 percent of brain tumors diagnosed in the United States.

In the study, researchers examined brain tumor samples from 206 patients. They found numerous gene mutations (changes) that occur in glioblastomas (more than 300 are already known). But they also found three genetic mutations that occur frequently but had not been recognized before. The team was also able to identify some of the main biological pathways that are disrupted in glioblastomas.

Johns Hopkins researchers published similar findings from a parallel but smaller study on the same day. “These are very exciting studies because they give us hope: Rather than having to fight the 300 or 400 known genetic defects in glioblastomas, we may be able to focus on far fewer to help us find the cause of these tumors,” Sloan says. “This would make the puzzle much easier to solve.”

Because most glioblastoma patients die within 14 months of being diagnosed, finding a cause of this deadly form of cancer could help doctors design treatments that would enable people to live longer.

Brain Tumor: International Study

Another large project, the Gliogene study, is the largest study to date of a primary brain tumor called a glioma. In the five-year study, an international team of researchers will try to identify what gene or genes are related to their development. A glioma is a common type of brain tumor that grows from nerve cells, called glial cells, which are important to brain tissue support.

If they can find those genes, they may be able to identify a genetic link among the relatives of people with brain tumors and use it to develop new treatment and perhaps improve existing ones. The hope is that one day the findings might even help researchers develop ways to prevent this kind of brain tumor.

The researchers’ goal is to screen more than 15,000 people around the world. Countries that are participating are the United States, United Kingdom, Sweden, Denmark and Israel. If you, or a member of your family, have a brain tumor and you are interested in participating in this study, visit Gliogene: An International Brain Tumor Family Study .

Brain Tumor: Rembrandt Is More Than a Painter

To do accurate research, scientists need a base of genetic information about brain tumors that is properly gathered and stored. Together, the NCI and National Institute of Neurological Disorders and Stroke (NINDS) have created such a database, the Repository for Molecular Brain Neoplasia Data (REMBRANDT). The repository will keep analyses of samples from brain tumors and other data on all types of brain tumors to provide researchers with invaluable information for their studies.

http://www.everydayhealth.com/brain-tumor/brain-tumor-causes.aspx

Ivy Foundation Featured on AZ Redbook

 

A Patient-Focused Approach

Catherine (Bracken) Ivy, founder and president of The Ben & Catherine Ivy Foundation, has traveled the world learning all she can about brain cancer – specifically, how to cure it.

She is determined, through the efforts of her foundation, to find better treatment options and improve the quality of life for patients with brain tumors, especially those with glioblastoma multiforme (GBM), the most common and aggressive form of malignant primary brain tumor. Ninety-eight percent of people diagnosed with GBM live fewer than 18 months.

Because brain cancer is rare compared to many other cancers, research into the disease receives little federal funding, pharmaceutical industry support or media attention. Today, standard of care currently involves removal of the tumor (though surgery most often fails to remove all the cancer) followed by radiation treatments and chemotherapy involving a drug with limited effect for the majority of patients. Sadly, little else remains to extend life expectancy or remission.

This status quo is not acceptable to Ivy. More than anything, she wants the Ivy Foundation to provide solutions – and hope – for people diagnosed with brain cancer.

“I want people with brain cancer and brain tumors to know that there is a community of people working very hard to try and help them,” Ivy says. “We’re not saying we’re going to cure it tomorrow, but a least we’re moving the needle. Our immediate goal is to double life expectancy in the next seven years for people diagnosed with brain cancer. We will never give up until we find a cure.”

Leading the charge

The Ivy Foundation’s overarching goal over the next seven years is to double the life expectancy of brain cancer patients from 18 to 36 months. And in working with TGen, Ivy says she has found three key values that align both organizations:

– Patient-focused research

– Conducting the best research possible in a cost-effective manner

– Making progress immediately

“Those three things are not simple,” Ivy says.

But, she says, the innovative ideas of TGen President and Scientific Director Dr. Jeffrey Trent make her believe her efforts are worthwhile. The two first met at a brain cancer conference in Tucson, and at subsequent meetings Trent outlined research that would help the Ivy Foundation achieve its goal of advancing patient care.

As a result, the Ivy Foundation recently granted $10 million to TGen: $5 million each for two new groundbreaking brain cancer projects.

Discovering why some patients live longer

One $5-million project is titled “Outliers in Glioblastoma Outcome: Moving the curve forward.” This five-year investigation seeks to discover why approximately 2 percent of GBM patients – the outliers – live far beyond the average survival time of 18 months.

“A major challenge with brain cancer is that people survive such a short time,” Ivy says. “If this research enables patients to live longer, clinicians and researchers will gain a better understanding of how this disease works, which will bring us time to study the disease, providing the opportunity to move closer to a cure.”

By precisely identifying the billions of molecular building blocks in each patient’s DNA through whole genome sequencing, TGen researchers hope to discover the genetic differences between those patients who survive only a few months and those who survive longer because their brain cancer develops more slowly.

Using these genetic targets, TGen researchers will identify those patients most likely to benefit from the current standard of care, and those who might best benefit from alternative or new experimental treatments.

First-in-patient clinical trials studies

In the second $5-million project, “Genomics Enabled Medicine in Glioblastoma Trial,” TGen and its clinical partners will lead first-in-patient clinical trial studies that will test promising new drugs that might extend the survival of GBM patients. This multi-part study will take place in clinics across the country and TGen laboratories.

This project begins with a pilot study of 15 patients, using whole genome sequencing to study their tumor samples to help physicians determine what drugs might be most beneficial.

To support molecularly informed clinical decisions, TGen labs also will examine genomic data from at least 536 past cases of glioblastoma, as well as tumor samples from new cases, developing tools that will produce more insight into how glioblastoma tumors grow and survive. TGen also will conduct a series of pioneering lab tests to measure cell-by-cell responses to various drugs.

To get new treatments to patients as quickly as possible, this five-year study will include a feasibility study involving up to 30 patients, followed by Phase II clinical trials with as many as 70 patients. TGen intends to team with the Ivy Early Phase Clinical Trials Consortium that includes the University of California, San Francisco; the University of California, Los Angeles; the MD Anderson Cancer Center; the Memorial Sloan Kettering Cancer Center; the University of Utah; and the Dana-Farber/Harvard Cancer Center.

The results of these clinical trials should not only help the patients who join them, but also provide the data needed for FDA approval and availability of new drugs that could benefit tens of thousands of brain cancer patients in the future.

“It’s a tremendous opportunity to find more solutions for the patient diagnosed with brain cancer,” says Ivy, who also is working to establish additional clinical trials in the Phoenix area, giving local patients more treatment options. “The clinical trials are very exciting because they can impact the patient today.”

More information about TGen

More information about The Ben & Catherine Ivy Foundation

–       Text by Steve Yozwiak, TGen senior science writer

–       Photo courtesy TGen

At top: Catherine Ivy, founder and president of The Ben & Catherine Ivy Foundation, with TGen Deputy Directors Dr. David Craig (left) and Dr. John Carpten (right)

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