Clinical Trials Test Treatments for High-Grade Brain Tumors


With a few exceptions, glioblastoma (GBM) remains largely incurable, and the U.S. Food and Drug Administration (FDA) has approved few treatments for the disease. Surgery (when feasible), radiation, and temozolomide are used in most patients. But even if a newly diagnosed tumor can be surgically excised, recurrences are too common.

In this blog post, I simply list some of the new treatments available in clinical trials for GBM and other high-grade brain tumors. Only drugs that have at least some preliminary results of activity are included, and the list is not meant to be fully comprehensive. The interested reader can judge for herself what might be of interest, keeping in mind that no single treatment is suitable or will work for all GBM patients. Continue reading…


Scientists Identify Key Defect in Brain Tumor Cells

Excerpt:

“In a new study, Yale researchers identified a novel genetic defect that prevents brain tumor cells from repairing damaged DNA. They found that the defect is highly sensitive to an existing FDA-approved drug used to treat ovarian cancer—a discovery that challenges current practice for treatment of brain tumors and other cancers with the same genetic defect, said the scientists.

“The study was published on Feb. 1 by Science Translational Medicine.

“Certain and leukemias have mutations in genes known as IDH1 and IDH2. The mutations render the cancers sensitive to treatment with radiation therapy or chemotherapy, significantly increasing the survival time for patients with the mutations. To better understand this sensitivity, a cross-disciplinary team of researchers led by Yale created models of the mutation in cell cultures.”

Go to full article.

If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our ASK Cancer Commons service.


Super Patient: Steven Keating Fights Brain Cancer with Data


In 2007, Steven Keating got his brain scanned for fun. “I volunteered for a study,” says Steven, who was then a student at Queen’s University in Canada. “I wanted to help science, and I was curious about seeing my brain.”

He saw more than anticipated—the magnetic resonance imaging (MRI) revealed a dime-sized abnormality in his left frontal lobe. But the researchers couldn’t tell what it was, and he had no adverse symptoms. “They said ‘don’t worry, keep an eye on it,'” Steven, who is now a Mechanical Engineering graduate student at the Massachusetts Institute of Technology (MIT) Media Lab, recalls. A follow-up scan in 2010 wasn’t worrisome either. Continue reading…


Gene Mutation May Lead to Treatment for Liver Cancer

Editor’s note: Cancer is caused by genetic mutations that lead to excess cell growth and tumor formation. Scientists have identified many specific cancer-causing mutations, and drugs have been developed to target and treat tumors with some of these specific mutations. Researchers recently discovered that two mutations—IDH1 and IDH2—can lead to the development of intrahepatic cholangiocarcinoma (iCCA). The discovery could open up new treatment options for some patients who have these mutations. Indeed, there are ongoing clinical trials testing new drugs in patients with IDH1 and IDH2 mutations.

“Two genetic mutations in liver cells may drive tumor formation in intrahepatic cholangiocarcinoma (iCCA), the second most common form of liver cancer, according to a research published in the July issue of the journal Nature.

“A team led by the Icahn School of Medicine at Mount Sinai and Harvard Medical School has discovered a link between the presence of two mutant proteins IDH1 and IDH2 and cancer. Past studies have found IDH mutations to be among the most common genetic differences seen in patients with iCCA, but how they contribute to cancer development was unknown going into the current effort.

“iCCA strikes bile ducts, tube-like structures in the liver that carry bile, which is required for the digestion of food. With so much still unknown about the disease, there is no first-line, standard of care and no successful therapies.

” ‘iCCA is resistant to standard treatments like chemotherapy and radiation,’ said Josep Maria Llovet, MD, Director of the Liver Cancer Program, Division of Medicine, Icahn School of Medicine at Mount Sinai, and contributing author. ‘Understanding the molecular mechanism of the disease is the key to finding a treatment that works.’ ”


Planned Clinical Phase I Trial to Examine the Safety of Vaccine Against Gliomas Based on Mutant IDH1 in Human Patients

“Astrocytomas and oligodendrogliomas are subtypes of a brain cancer called ‘glioma’. These incurable brain tumors arise from glial cells, a type of support cell found in the central nervous system. ‘Low-grade gliomas’, which grow comparatively slowly, spread in a diffuse manner across the brain and are very difficult to completely eliminate through surgery. In many cases, the effectiveness of treatments with chemotherapy and radiotherapy is very limited. Gliomas can develop into extremely aggressive glioblastomas.

“Low-grade gliomas have a particular feature in common: more than 70% of the cases exhibit the same gene mutation in tumor cells. An identical ‘typo’ in the DNA causes the exchange of a single, specific protein building block (amino acid) in an enzyme called isocitrate dehydrogenase 1 (IDH1). As a result, most cancer cells do not follow the original building plan for the protein; at the 132nd position in the molecule’s sequence, they insert the amino acid histidine instead of arginine…

” ‘…we might be able to use a vaccine to alert the patient’s immune system to mutant IDH1, fighting the tumor without damaging healthy cells,’ [Prof. Dr. Michael Platten at the German Consortium for Translational Cancer Research] explains.

“In collaboration with a team of physicians and scientists from Heidelberg University Hospital, DKFZ and the Universities of Mainz, Tübingen and Hamburg, Platten and his co-workers have now made the first successful step toward a vaccine that specifically targets the mutation in the tumor.

“In a clinical trial scheduled to start early next year, with the support of the German Consortium for Translational Cancer Research (DKTK), they plan to examine the safety of the vaccine against gliomas based on mutant IDH1 in human patients, for the first time.”

Editor’s note: Early next year, oncologists will begin testing a newly developed cancer vaccine in a clinical trial with volunteer patients, in the hopes that it will help treat low-grade gliomas. Cancer vaccines are a type of immunotherapy treatment; they boost a patient’s own immune system to fight cancer. The new vaccine takes advantage of a dysfunctional protein that is found in 70% of low-grade gliomas. The protein is called IDH1, and the vaccine is designed to alert the patient’s immune system to attack cells with mutant IDH1, potentially shrinking the brain tumor. So far, the vaccine has only been tested in mice, but the results were promising.


Isocitrate Dehydrogenase 1 Is a Novel Plasma Biomarker for the Diagnosis of Non–Small Cell Lung Cancer

We previously showed that isocitrate dehydrogenase 1 (IDH1) is significantly increased in NSCLC tumors. This study aimed to examine the plasma levels of IDH1 in a large patient population to evaluate its effectiveness in NSCLC diagnosis.

IDH1 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly lung adenocarcinoma, with relatively high sensitivity and specificity.