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Cellular target may prove useful in treating deadly brain tumors
April 06, 2009DURHAM, N.C. - Duke University researchers have identified a receptor on the surface of cells that may give them another avenue of attack against glioblastoma, the most common and most deadly type of brain cancer.
The neurokinin 1 receptor (NK1R), which may be expressed in all human glioblastoma cells, may prove to be an appropriate target for therapies aimed at treating these brain tumors, according to a study led by researchers in the Duke Department of Anesthesiology and the Preston Robert Tisch Brain Tumor Center at Duke.
"There are some previously identified cellular targets for therapy which are now being investigated in clinical trials, and the findings from our research represent potential alternate or complementary targets that may help patients facing this devastating disease," said Madan Kwatra, PhD, a researcher in Duke's department of anesthesiology, and senior investigator on this study. "Patients generally die from the disease within 18 months of glioblastoma diagnosis."
The results of the study were published in the March 30, 2009 online edition of the Journal of Neurochemistry. The study was funded by the National Institutes of Health.
The researchers examined stimulation of the receptor NK1R in human glioblastoma cells growing in a dish, and found that activation of NK1R led to the activation of Akt, a cellular protein that suppresses the natural cell death process.
"In human cancers, this would translate into a proliferation of cancer cell growth," said Kwatra.
The researchers also showed that blocking NK1R activity reduced Akt activity, which then led to greater cell death.
"This finding suggests that if we are able to block NK1R activity, we may have a better shot at stalling cancer growth," Kwatra said.
A previous study showed NK1R activity in 10 out of 10 glioblastomas and nine out of 12 astrocytomas, a lower-grade malignant brain tumor.
Current therapies to treat glioblastomas are directed toward blocking the activity of another cellular receptor called epithelial growth factor receptor (EGFR). A recent clinical trial using an EGFR inhibitor found that patients whose tumors expressed high levels of phosphorylated - or chemically altered - Akt did not respond to treatment, Kwatra said.
"This underscores the importance of discovering the origin of active Akt in glioblastomas," he said. "We propose that the elevated levels of phosphorylated Akt may come from active forms of NK1R, and it's possible that a better response might be obtained by simultaneously blocking EGFR and NK1R."
Future studies may examine the role of a NK1R inhibitor in glioblastoma patients, perhaps as a corollary to treatment with an EGFR blocker such as erlotinib, which is currently being studied in clinical trials.
"The FDA has already approved a drug for combating chemotherapy-induced nausea and vomiting that happens to be an NK1R inhibitor, so that might be a possibility for study in conjunction with erlotinib," Kwatra said.
Duke University Medical Center
The results of the study were published in the March 30, 2009 online edition of the Journal of Neurochemistry. The study was funded by the National Institutes of Health.
The researchers examined stimulation of the receptor NK1R in human glioblastoma cells growing in a dish, and found that activation of NK1R led to the activation of Akt, a cellular protein that suppresses the natural cell death process.
"In human cancers, this would translate into a proliferation of cancer cell growth," said Kwatra.
The researchers also showed that blocking NK1R activity reduced Akt activity, which then led to greater cell death.
"This finding suggests that if we are able to block NK1R activity, we may have a better shot at stalling cancer growth," Kwatra said.
A previous study showed NK1R activity in 10 out of 10 glioblastomas and nine out of 12 astrocytomas, a lower-grade malignant brain tumor.
Current therapies to treat glioblastomas are directed toward blocking the activity of another cellular receptor called epithelial growth factor receptor (EGFR). A recent clinical trial using an EGFR inhibitor found that patients whose tumors expressed high levels of phosphorylated - or chemically altered - Akt did not respond to treatment, Kwatra said.
"This underscores the importance of discovering the origin of active Akt in glioblastomas," he said. "We propose that the elevated levels of phosphorylated Akt may come from active forms of NK1R, and it's possible that a better response might be obtained by simultaneously blocking EGFR and NK1R."
Future studies may examine the role of a NK1R inhibitor in glioblastoma patients, perhaps as a corollary to treatment with an EGFR blocker such as erlotinib, which is currently being studied in clinical trials.
"The FDA has already approved a drug for combating chemotherapy-induced nausea and vomiting that happens to be an NK1R inhibitor, so that might be a possibility for study in conjunction with erlotinib," Kwatra said.
Duke University Medical Center
Glioblastoma Current Events and Glioblastoma News RSSResearchers Identify Role of Gene in Tumor Development, Growth and Progression
Virginia Commonwealth University Massey Cancer Center and VCU Institute of Molecular Medicine researchers have identified a gene that may play a pivotal role in two processes that are essential for tumor development, growth and progression to metastasis.
Cancer metabolism discovery uncovers new role of IDH1 gene mutation in brain cancer
Agios Pharmaceuticals today announced that its scientists have established, for the first time, that the mutated IDH1 gene has a novel enzyme activity consistent with a cancer-causing gene, or oncogene.
Angiochem crosses BBB, shows safety, efficacy in phase 1/2 brain cancer studies
Angiochem, Inc. a clinical-stage biotechnology company developing drugs that are uniquely capable of crossing the blood-brain barrier to treat brain diseases, announced today that its lead drug candidate, ANG1005, has demonstrated a favorable safety and efficacy profile in more than 100 patients with brain cancer from two separate Phase 1 /2 clinical studies in patients with progressive gliomas, including recurrent glioblastoma, and in patients with progressive brain metastases.
NEDD9 Protein Supports Growth of Aggressive Breast Cancer
Researchers at Fox Chase Cancer Center have demonstrated that a protein called NEDD9 may be required for some of the most aggressive forms of breast cancer to grow. Their findings, based on the study of a mouse model of breast cancer, are presented in a recent issue of Cancer Research, available on-line now.
Toward a nanomedicine for brain cancer
In an advance toward better treatments for the most serious form of brain cancer, scientists in Illinois are reporting development of the first nanoparticles that seek out and destroy brain cancer cells without damaging nearby healthy cells.
GEN reports on expanding NextGen sequencing applications
Next-Generation Sequencing (NGS) technologies are not only beginning to supplant traditional Sanger sequencing methodology but are also giving DNA microarrays a run for the money as well, reports Genetic Engineering & Biotechnology News (GEN).
Avastin dramatically improves response, survival in deadly recurrrent glioblastomas
The targeted therapy Avastin, alone and in combination with the chemotherapy drug CPT-11, significantly increased response rates, progression-free survival times and survival rates in patients with a deadly form of brain cancer that had recurred.
Why don't brain tumors respond to medication?
Malignant brain tumors often fail to respond to promising new medication. Researchers in Heidelberg have discovered a mechanism and a tumor marker for the development of this resistance.
NIH researchers identify key factor that stimulates brain cancer cells to spread
Researchers funded by the National Institutes of Health have found that the activity of a protein in brain cells helps stimulate the spread of an aggressive brain cancer called glioblastoma multiforme (GBM).
Anti-psychotic drugs could help fight cancer
The observation that people taking medication for schizophrenia have lower cancer rates than other people has prompted new research revealing that anti-psychotic drugs could help treat some major cancers.
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