brain cancer Archives - NFCR

brain cancer

Attacking Metastatic Tumors in the Brain

Targeting HER3 could cripple metastatic cancers that have spread to the brain.

(Bethesda, MD, June 5, 2017) Rakesh Jain, PhD, Director of the Edwin L. Steele Laboratory for Tumor Biology at the Massachusetts General Hospital and supported by the National Foundation for Cancer Research, has discovered a novel mechanism behind the resistance to HER2- or PI3K-targeted therapies, and a treatment strategy that may overcome treatment resistance. This significant finding was reported in the latest issue of the journal Science Translational Medicine.

Rakesh Jain’s discovery could be very important for cancer patients whose cancers have spread to the brain.  About 20% to 25% of all breast cancers have an excess of a protein known as Human Epidermal Growth Factor Receptor 2 (HER2). HER2-positive (HER2+) breast cancer spreads more quickly than other types of breast cancer, and while several targeted therapies are now available to treat HER2+ breast cancer, putting this cancer into remission for years or longer in many patients, up to 50% of patients treated with these targeted therapies eventually develop brain metastases, which are inevitably fatal.

This research project directed by Dr. Jain may have unlocked a key as to why brain metastases are resistant to HER2+ targeted therapies, and have uncovered a potential treatment strategy to overcome this resistance.

Using tumor models and human cancer samples, the researchers found an overexpression of Human Epidermal Grown Factor Receptor 3 (HER3) in breast cancer-associated brain lesions, and that inhibiting HER3 could help overcome treatment resistance.  Dr. Jain’s team found that using drugs that target HER3 combined with those that target HER2 significantly slowed brain metastatic tumor growth and improved survival of the tumor models.  These results are the collaborative efforts between Rakesh Jain and Jeffrey A. Engelman, MD, PhD,  Global Head of Oncology at the Novartis Institutes for BioMedical Research (formerly with the MGH Cancer Center), an expert in targeted therapies and co-senior author of the publication.

Cancer therapies that target specific proteins often fail to reign in tumors that have metastasized to the brain, and Rakesh Jain’s collaboration with Jeffrey Engelman could well have revealed the mechanism behind therapeutic resistance of brain metastases in HER-2 positive breast cancer.  This breakthrough research “has identified new treatment strategies to overcome this problem which is often lethal to the patients,” says Dr. Jain. “We believe our discovery could have a substantial impact on the future development of therapeutic strategies and ultimately, patient survival from this deadly disease.”

Dr. Jain hopes that clinical trials and future therapeutic strategies for metastatic breast cancer will include HER3 targeted therapies in treating brain metastasis in HER2+ (or PIK3CA mutant) breast cancer.  And since HER3 has been associated with treatment resistance in several types of cancer, this discovery could potentially benefit a much broader group of patients.

“The impact of the microenvironment on tumor growth is a major focus of Rakesh Jain’s research, and NFCR is proud to have supported his research since 1998,” says Franklin C. Salisbury, Jr., Chief Executive Officer of NFCR.  Research cures cancer, and “NFCR’s support of outstanding scientists like Rakesh Jain is making possible whole new approaches to treating cancer, giving hope and promise to patients with cancer.”

About the National Foundation for Cancer Research

The National Foundation for Cancer Research (NFCR) is a leading cancer research charity dedicated to funding cancer research and public education relating to cancer prevention, earlier diagnosis, better treatments and, ultimately, a cure for cancer. NFCR promotes and facilitates collaboration among scientists to accelerate the pace of discovery from bench to bedside. NFCR is committed to Research for a Cure – cures for all types of cancer. For more information, visit http://www.nfcr.org/ or call (800) 321-CURE (2873).

Media Contact:
Hali Hartmann
443 474 6294
hhartmann@nfcr.org

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Meet Carmen Rice: A Courageous and Inspirational GBM Survivor

This year marks the 13th anniversary of Carmen Rice’s survival from Glioblastoma Multiforme (GBM) – the deadliest brain cancer that is widely regarded as incurable and universally fatal. GBM kills 91% of patients within three years of diagnosis and NFCR is part of a robust, international coalition working on innovative ways to research the disease. In the cancer research world, too often stories do not have optimistic endings, which is why our work continues until we find cures. Yet Carmen’s thirteen-year survival is nothing less than miraculous and we are truly honored to share her incredible story with you.

Carmen’s Story

In 2004, Carmen Rice began experiencing severe headaches, nausea and dizziness.  She remembers having lunch in a local restaurant and a moment later waking up in the hospital bed not knowing what happened or how she got there. She had a grand mal seizure.  Scans revealed a small brain tumor.  Days later, Carmen underwent brain surgery to remove the tumor.

The tumor removed proved to be GBM, a very aggressive, malignant tumor. Carmen was told she had only six months to live. Terrified, yet determined to beat this, she began an aggressive treatment regimen of radiation and chemotherapy.

Carmen remained in remission until 2008, when during a routine check-up, a new growth appeared in the same site as the original tumor. Since GBMs tend to return to the same site as the original tumor, Carmen and her doctors assumed this was a recurrence. In December 2008, Carmen underwent her second brain surgery. She spent Christmas and New Year’s in the hospital praying that she would once again recover. Her prayers were answered when the final pathology reported that this new growth was not malignant.
“There are amazing new discoveries being made each day. Thank you NFCR, donors, advocates, doctors and scientists for saving the lives of so many people like me. You give me hope and inspiration to move forward.” –Carmen Rice

(Left to Right) NFCR CEO Franklin C. Salisbury, Jr., NFCR President Dr. Sujuan Ba, Carmen Rice and Darrell Rice.

Fast forward to today, Carmen continues to live a happy, healthy and active life. She enjoys every moment and is an enthusiastic speaker within the cancer community, inspiring others with her positive outlook and message of hope. Carmen talks about how grateful she is to NFCR for the groundbreaking research done in the GBM field.

In her latest speech about her survival story, Carmen passionately discussed NFCR and her support of our work – specifically GBM AGILE.  Carmen is confident – as are we – that together we will find a cure for GBM.

Today’s Research Will Lead to Tomorrow’s Cures

GBM AGILE

Led by the best and brightest cancer researchers, GBM AGILE is a revolutionary global collaboration to test and develop new brain cancer treatments.  Its personalized approach will allow us to accelerate the discovery of targeted treatments for individual patients.

This global coalition has attracted over 150 participants from more than 40 leading cancer institutions across three continents. It implements a new generation of clinical trials – called “adaptive trials” – which allow patients to be enrolled more quickly, receive treatment with multiple anti-cancer drugs simultaneously and does not require years of follow-up to determine whether a new experimental treatment is beneficial. This revolutionary approach accelerates research for curing the aggressive form of cancer GBM and will serve as a new clinical research model for combating other cancers as well. As a founding member of the coalition, NFCR has continued to take a leading role in this unprecedented effort. It is anticipated that patient enrollment may start in the fall of 2017. Stayed tuned!

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4 Must-Know Facts About the Deadliest Brain Tumor

Glioblastoma multiforme- also known as GBM– is the most lethal form of brain cancer in adults. This devastating brain cancer spreads into other parts of the brain very quickly and is usually not surgically curable. Typically, radiation and chemotherapy are given with the hopes of delaying tumor progression. If you or a loved one is diagnosed with GBM, here are 4 important facts you need to know:

Brain Tumor Statistics

  • GBM kills 95% of patients within five years of diagnosis, with more than half dying within the first 15 months after diagnosis.
  • Although GBM can occur in any age group, it is most common in adults between the ages of 45-70.[i]
  • This year, more than 12,000 people living in the U.S. and tens of thousands more worldwide will receive a diagnosis of GBM. [ii]

1. Connect with a doctor(s) who specializes in GBM.

As with any rare or aggressive cancer, it’s best to seek care from a doctor who spends all of his or her time treating that particular disease. When it comes to GBM, there are many nuances to both its diagnosis and treatment that require expert knowledge.  Second opinions are also extremely important as they will either confirm what you’ve already been told or present different options to weigh.

2. Know the facts.

GBMs are extremely complex tumors.  Complete surgical removal of the entire tumor is extremely difficult because these tumors have finger-like tentacles that extend into surrounding normal brain tissue.  GBMs are also made up of a wide mix of different cell types that often differ from patient to patient.  Additionally, when GBMs recur or grow back—and they almost always do–the molecular profile of the tumor changes dramatically.  As a result, response to treatment varies considerably and today’s five-year survival for GBM is less than 5%.

3. With GBM AGILE, the future looks promising.

Currently there is no cure for GBM.  Although there have been hundreds of standard clinical trials for GBM, survival rates for patients with GBM have not improved in any meaningful way in more than 30 years… GBM AGILE brings tremendous hope to patients battling GBM today.

What is GBM AGILE?

Over 150 researchers from more than 40 leading cancer institutions across four continents have come together to find cures for GBM by launching the first-ever global, adaptive clinical trial that will revolutionize how brain cancer treatments are tested and developed. This new type of clinical trial platform is called GBM Adaptive Global Innovative Learning Environment, or GBM AGILE for short. By offering the ability to access to the newest, most promising treatments quickly and in real-time, GBM AGILE will provide people living with brain cancer new hope where little currently exists. While adaptive trials are not yet commonplace, Congress and the FDA are focused on accelerating their development to benefit patients, including GBM AGILE.

4. NFCR is attacking GBM head on.

With GBM AGILE, medical research is being transformed right now by the biggest global collaboration in the history of brain cancer research. NFCR has provided seed funding for this revolution and as part of the executive steering committee, is helping to develop and manage this groundbreaking adaptive trial protocol.

The GBM AGILE team is currently in discussion with the USA’s FDA (Food and Drug Administration) to create a process that will make it faster for patients to access the promising drugs that are being tested in this clinical trial. This will be done by allowing seamless transition from Phase II to Phase III of the trial which does not traditionally happen in the current clinical trial format. The protocol is nearly complete, and patient enrollment is expected to begin in January, 2018 giving patients worldwide the best chance to treat their disease.

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7 Facts You Need to Know About Brain Tumors

What is Brain Tumor?

  • Of the nearly 80,000 brain tumors diagnosed in the U.S. each year, approximately 32% are considered malignant – or cancerous.
  • Overall, the chance that a person will develop a malignant tumor of the brain or spinal cord in his or her lifetime is less than 1%.
  • Glioblastoma multiforme (GBM) is the deadliest type of brain cancer, accounting for 45% of all malignant brain tumors.

Here’s a list of seven facts you need to know about brain tumors. And make sure you read about the work NFCR is doing to combat the deadliest brain cancer with GBM AGILE.

1. Primary brain cancer is rare.

primary malignant brain tumor is a rare type of cancer accounting for only about 1.4% of all new cancer cases in the U.S.  The most common brain tumors are known as secondary tumors, meaning they have metastasized, or spread, to the brain from other parts of the body such as the lungs, breasts, colon or prostate.

2. The cause of brain cancer is usually unknown.

Most people diagnosed with a primary brain tumor do not have any known risk factors. However, certain risk factors and genetic conditions have been shown to increase a person’s chances of developing one, including:

  • The risk of a brain tumor increases as you age.
  • People who have been exposed to ionizing radiation—such as radiation therapy used to treat cancer and radiation exposure caused by atomic bombs– have an increased risk of brain tumor.[i]
  • Rare genetic disorders like Von Hippel-Lindau disease, Li-Fraumeni syndrome, and Neurofibromatosis (NF1 and NF2) may raise the risk of developing certain types of brain tumors. Otherwise, there is little evidence that brain cancer runs in families.[ii]

3. Typically brain tumors don’t have obvious symptoms.

Headaches that get worse over time are a symptom of many ailments including brain tumors. Other symptoms may include personality changes, eye weakness, nausea or vomiting, difficulty speaking or comprehending and short-term memory loss.

Even benign or non-cancerous tumors can be serious and life threatening. If you experience these symptoms, speak with your doctor right away. 

4. Brain tumors can occur at any age.

Primary brain tumors—those that begin in the brain—can develop at any age, but they are most common in children and older adults. While brain tumors are one of the most common cancers occurring in children 0-14 years, the average age of diagnosis is 59 years. [iii]

5. Cell phones aren’t proven to cause brain cancer.

Although long-term studies are ongoing, to date there is no definitive evidence that cell phone use increases the risk of cancer. However, if you are concerned about the possible link between cellphones and cancer, consider limiting your use of cellphones — or use a speaker or hands-free device.

6. Survival rates vary.

There are different types of primary brain cancer and survival rates vary significantly depending on the type of cancer. Some types of brain cancer, such as meningioma, anaplastic ependymoma and oligodendroglioma, are highly treatable, while others are less responsive to treatment.

7. With GBM AGILE, the future looks promising.

Glioblastoma multiforme (also known as GBM) is the deadliest of all (primary) brain cancers and is widely regarded as incurable and universally fatal, killing 95% of patients within five years of diagnosis.

To combat this deadly disease, NFCR is part of a robust, international coalition working on innovative ways to defeat GBM utilizing a rigorous adaptive trial platform known as GBM AGILE (Adaptive Global Innovative Learning Environment).  Led by some of the best and brightest brain cancer researchers in the world, GBM AGILE is re-engineering the way clinical trials are conducted to develop more effective treatments faster than ever before.

To learn more about adaptive clinical trials and GBM AGILE, click here.

In addition to specific projects listed below, genomics research is helping us attack brain cancers – and all types of cancer. NFCR has distinguished itself from other organizations by emphasizing long-term, transformative research and working to move people toward cancer genomics.

Dr. Rakesh Jain is a leader in the field of tumor biology – specifically in anti-angiogenic therapy, which looks at thwarting certain types of blood vessel formation. Dr. Jain has been studying the role angiogenesis plays in glioblastoma multiforme (GBM), the deadliest form of brain cancer. Dr. Jain’s research is helping doctors better tailor the use of anti-angiogenic therapies by identifying the characteristics that cause resistance for GBM patients. Dr. Jain and his team have identified molecular resistance pathways that may direct the development of new drugs that target these pathways and could extend the benefits of anti-angiogenic therapies for patients.
Because GBM invades healthy tissues near the tumor, Dr. Jain’s current NFCR-funded research is focused on testing inhibitors that could prevent invasion. Vessel co-option is a process by which cancer cells migrate through and around nearby healthy tissue. Dr. Jain is identifying genes and pathways that facilitate vessel co-option in order to prevent invasion and improve GBM therapies.

The Director of NFCR’s Scientific Advisory Board, Dr. Web Cavenee, has partnered with NFCR-funded scientist Dr. Paul B. Fisher to discover a new pharmacological agent that could – with additional chemistry – lead to a new drug to prevent radiation-induced invasion of GBM cells. The researchers have tested their pharmacological agent in combination with radiation and have seen profound survival benefits in pre-clinical models.

Previously NFCR-funded scientist Dr. W.K. Alfred Yung’s research focused on drugs that target a gene called PI3K, which is a key factor in about 30% of GBM cases. His team collected glioma stem cells (GSCs) from GBM patients and developed a special panel of cell lines to investigate patterns of resistance to P13K inhibitors. The researchers are figuring out the molecular profile of these GSCs to identify potential targets for drug development. Results from the P13K studies have shown that the molecular profile of GSCs contain increased levels of Wee-1, which is a protein that controls cell division and growth. Following these results, the team then combined a P13K inhibitor with a Wee-1 inhibitor and found there was a greater inhibition of cell growth and the cancer cells were induced into cell suicide. Plus, when they tested the same inhibitors on complex GBM tumor models, they discovered similar benefits. These findings reveal molecular targets and designs for combination therapies that could lead to new treatments for GBM patients.

 

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[1] http://www.mayoclinic.org/diseases-conditions/brain-tumor/symptoms-causes/dxc-20117134

[2] http://www.cancercenter.com/brain-cancer/risk-factors/

[3] http://www.abta.org/about-us/news/brain-tumor-statistics/?referrer=https://www.bing.com/

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Understanding Adaptive Clinical Trials

Testing new treatments is key to successfully treating cancer. Unfortunately, the current model for conducting clinical trials — evaluating the effectiveness of therapies on human subjects — is inefficient, expensive and suffers from high failure rates. To overcome these challenges, the practice of adaptive trials is emerging and has become one of the most promising advancements in cancer research today.

Challenges with traditional clinical trials

Currently, it takes approximately $2.5 billion dollars, 10+ years and thousands of patient volunteers to bring one drug to market.[i] Despite this high cost, over half of phase III oncology trials have negative results or fail to complete. In addition, traditional trials cannot be modified once they begin. Patients get only one opportunity and receive only one treatment.

Adaptive trials literally adapt as evidence accumulates

Adaptive trials do not require years of follow-up to determine whether a new experimental treatment is beneficial. They test multiple treatments and combinations of treatments on patients in parallel and are designed to be continuously updated as researchers use what they learn from each patient to make real-time adjustments as the trial proceeds.

They are flexible by design so adjustments can be made in terms of dosage, subject population or sample size as needed.

In an adaptive trial, if one treatment regimen seems to be more successful, researchers can increase the number of participants receiving that treatment. This is especially important for patients with aggressive cancers as life expectancies are too short for traditional trial timetables. With adaptive trials, ineffective treatments can be shut down early, and new treatments can be initiated quickly enabling patients to receive the most promising treatments faster.

In a latest article published on Science Magazine: “Congress and FDA nominee heap love on ‘adaptive trials”, GBM AGILE is featured as one of the ongoing clinical trials using this new adaptive trial design.

GBM AGILE revolutionizes brain cancer trials

Glioblastoma multiforme (also known as GBM) is the deadliest brain cancer and is widely regarded as incurable and universally fatal, killing 95% of patients within five years of diagnosis. To combat this deadly disease, NFCR is part of a robust, international coalition working on innovative ways to defeat GBM utilizing adaptive trials known as GBM AGILE.

Led by the best and brightest cancer researchers, GBM AGILE is a revolutionary global collaboration to test and develop new brain cancer treatments. Its personalized approach will allow us to accelerate the discovery of targeted treatments for individual patients. This global coalition has attracted over 150 participants from more than 40 leading cancer institutions across three continents. This revolutionary approach accelerates research for curing the aggressive form of brain cancer GBM and will serve as a new clinical research model for combating other cancers as well.

In addition to GBM AGILE, there are other adaptive trials underway for certain cancers and tumor types, with more coming soon.  Other trials include:

  • I-SPY TRIAL is an adaptive clinical trial for women with newly diagnosed, locally advanced breast cancer.
  • Lung-MAP is a large adaptive clinical trial testing several new treatments for patients who have advanced stage squamous cell lung cancer.
  • Precision Promise is the first large-scale precision medicine adaptive trial for patients with pancreatic cancer.

While adaptive trial features are not yet commonplace, Congress and the FDA are focused on accelerating their development to benefit patients.

[i] https://www.scientificamerican.com/article/cost-to-develop-new-pharmaceutical-drug-now-exceeds-2-5b/

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NFCR’s Genomics Newsroom: New genes linked to increased risk of ovarian and brain cancer

What is “genomics”?

Cancer develops when genetic material (DNA) becomes damaged or changed. We know some cancer causing genetic changes are acquired (i.e. smoking), while others are inherited. Studying cancer genomics explores the differences between cancer cells and normal cells. Advances in understanding how cancer behaves at a genomic and molecular level is helping doctors treat cancer “smarter”.

12 new genes identified that drive ovarian cancer

Ovarian cancer is a leading cause of death for women worldwide. The estimated five-year survival rate for patients whose ovarian cancer is detected early is about 93%. However, only 15% of women are diagnosed at the early stages when treatment is most successful. Ovarian cancer can be difficult to diagnose because initial symptoms are similar to gastrointestinal illness and indigestion.

Using a novel genotyping technique, an international team of scientists from the United Kingdom, the U.S. and Australia analyzed the DNA of almost 100,000 people, including 17,000 patients with the most common type of ovarian cancer. Their findings revealed 12 new genetic variants that raise the likelihood of developing ovarian cancer and could eventually help doctors predict someone’s chances of developing this disease with greater accuracy and/or treat it with greater success.

13 new gene mutations identified that drive brain cancer

Another study led by scientists at the Institute of Cancer Research in the UK uncovered 13 new gene mutations linked to increased risk of glioma- the most common form of brain cancer. One of the genetic changes discovered increases risk of brain cancer by as much as 33%, with the rest by at least 15%. These findings are significant as currently there are no effective means to detecting brain cancer early – and this may provide researchers the chance to understand more about how brain cancer develops and how we may one day best treat it, or even prevent it.

Genomics research is helping us attack these cancers – and all types of cancer. NFCR has distinguished itself from other organizations by emphasizing long-term, transformative research and working to move people toward cancer genomics. To learn more about specific research by NFCR-funded scientists, click here.

 

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New Treatment for Glioblastoma Multiforme Developed by NFCR Scientists

Dr. Web Cavenee and Dr. Paul Fisher Publish Report Titled “Inhibition of radiation-induced glioblastoma invasion by genetic and pharmacological targeting of MDA-9/Syntenin”

 

NFCR congratulates Dr. Web Cavenee and Dr. Paul B. Fisher on their discovery of a new pharmacological agent to treat glioblastoma multiforme (GBM), the deadliest brain cancer, which they have been developing together with NFCR support.

GBM Cavenee and Fisher Report This new pharmacological agent could – with additional chemistry – lead to a new drug to prevent radiation-induced invasion of GBM cells. The researchers have tested their pharmacological agent in combination with radiation with profound survival benefits in pre-clinical models. Click here to read the full report by the scientists.

Paul B. Fisher, M.Ph., Ph.D., Director of the Virginia Commonwealth University’s (VCU) Institute of Molecular Medicine (VIMM), focuses on cancer genetics and Web Cavenee Ph.D., Director of the Ludwig Institute for Cancer Research at the University of California at San Diego focuses on GBM. An exciting breakthrough for the treatment of GBM, this is about collaboration between two scientists on opposite coasts and shows how NFCR research may lead to tangible therapies for multiple cancers.

NFCR has been funding Dr. Fisher’s research since 2008, and Dr. Cavenee’s research starting in 2002. “NFCR scientists are making headway in the fight against one of the most aggressive form of cancer, GBM, by working together on vital pre-clinical models,” said Franklin C. Salisbury, Jr., NFCR CEO. “For years, discoveries from NFCR-funded research have led to better treatments today – and this latest discovery by two incredibly talented scientists gives us proof there will be improved therapies for GBM and multiple cancers in the foreseeable future.”

 

About the Scientists

Dr. Paul B. FisherDr. Paul B. Fisher, M.Ph., Ph.D. is the Director of the VCU Institute of Molecular Medicine at the VCU School of Medicine and is a professor and Chair of Human and Molecular Genetics at the VCU School of Medicine. Dr. Fisher’s laboratory focuses on understanding the molecular and biochemical basis of cancer etiology and progression with an emphasis on translating this information to develop improved methods for diagnosing, staging and treating cancer. Read more about Dr. Fisher on NFCR’s scientist page and VCU’s website. Dr. Fisher was the Virginia Outstanding Scientist of the Year in 2014.

 

 

 

Dr. Web CaveneeDr. Web Cavenee, Ph.D., formerly an NFCR-funded research Fellow and Director of the Ludwig Institute for Cancer Research (LICR) at UCSD, is now Chairman of NFCR’s Scientific Advisory Board and Director of Strategic Alliances, Central Nervous System Tumors at LICR UCSD. His pioneering research has led to groundbreaking discoveries that have fundamentally changed our understanding of the molecular mechanisms that drive the growth, migration, and survival of glioblastoma multiforme cells—leading to potential new therapeutic approaches for treating GBM. Dr. Cavenee was recently awarded the 2016 Feldman Founder’s Award for Adult Brain Tumor Research from the National Brain Tumor Society. Read more about Dr. Cavenee and the NFCR’s Scientific Advisory Board.

 

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