Thema: Presse: Targeted treatment for brain cancer shows promise
Presse: Targeted treatment for brain cancer shows promise
Tina[a]
29.11.2005 18:19:59
Targeted treatment for brain cancer shows promise
By Joie Guner
Genetic analysis of patients with brain cancer can be used to provide drug therapy which will maximally benefit them in treatment, according to a UCLA study published this month.
A UCLA Jonsson Cancer Center research group conducted a multidisciplinary study of glioblastoma, a lethal malignant brain tumor, and discovered molecular signatures in the tumors that can be used to tailor drug therapy to patients for maximum benefit.
The paper was published on Nov. 10 in the New England Journal of Medicine.
Paul Mischel, a professor of pathology at the Jonsson Cancer Center and lead researcher, said getting the right drugs to the right patients is a challenge.
"There is a new kind of approach to treating cancer which is based on targeted molecular therapy as opposed to the more traditional approach to cancer therapy," Mischel said.
"This is really going to be the future of cancer research and, in fact, UCLA is a critical player in making that happen," he said.
On average, people who have glioblastoma survive less than a year after the initiation of tumor growth, researchers said.
The proliferation of cancer cells, leading to the brain tumor glioblastoma, is linked to the overexpression of the mutant form of epidermal growth factor receptor, EGFRvIII. Epidermal growth factor receptor (EGFR) is a cell surface protein that is involved in cellular division and cell growth.
The research group studied patients who were treated with drug therapies such as Tarceva and Iressa, which block the signals causing EGFR to become active. The scientists noticed that some patients responded positively to the drug therapies while others did not.
The group found that patients who had both the mutant receptor protein EGFRvIII and the tumor repressor protein, called PTEN, responded more effectively to the drug therapies than patients who did not. Of the patients who underwent drug therapy, the 10 to 20 percent of patients who possessed this molecular signature lived five times longer than the patients who did not. The molecular markers, EGFRvIII and PTEN, were specifically found to be targeted by signal blocker drugs of EGFR.
An independent study of patients at UC San Francisco as well as in brain tissue cells also confirmed the findings.
Treatments for the brain cancer help to extend survival time but there is no cure for the cancer.
"The therapies for glioblastoma patients are not very good. (Using molecular signatures) you can maximize the treatment effect and minimize the unnecessary toxicity," said Maria Wang, a postdoctoral fellow in Mischel´s lab.
Based on molecular signatures, researchers can identify which patients will not respond to signal blockers of EGFR and hence not put these patients through ineffective toxic cancer treatments.
"Nobody has been cured of this (type of cancer) yet. The great thing is that clearly some of the patients benefit from this targeted treatment," said Ingo Mellinghoff, assistant professor in the department of molecular and medical pharmacology.
"This is the first time a highly targeted treatment ... has had substantial impact on the growth of this aggressive tumor," he said.
Further research is being conducted to understand how treatment works.
"(Future research involves) understanding how different components within the tumor will respond to these drugs so we can figure out how to rationally combine drugs to better treat these patients," Mischel said.
The researchers also want to study the patients who didn´t respond to the EGFR signal blocking drugs to determine which therapies are most effective for them.
"We now have a rough idea of what percentage will respond to this treatment and we can select patients who are more likely to respond to it and then understand how we can overcome the ultimate failure of the therapy," Mellinghoff said.
This study can affect the way that cancer therapies are diagnosed to treat patients, using molecular signatures to specifically treat patients, researchers said.
"This helps to begin to figure out how to develop rational or smart combination of drugs to help treat these patients," Mischel said.
By Joie Guner
Genetic analysis of patients with brain cancer can be used to provide drug therapy which will maximally benefit them in treatment, according to a UCLA study published this month.
A UCLA Jonsson Cancer Center research group conducted a multidisciplinary study of glioblastoma, a lethal malignant brain tumor, and discovered molecular signatures in the tumors that can be used to tailor drug therapy to patients for maximum benefit.
The paper was published on Nov. 10 in the New England Journal of Medicine.
Paul Mischel, a professor of pathology at the Jonsson Cancer Center and lead researcher, said getting the right drugs to the right patients is a challenge.
"There is a new kind of approach to treating cancer which is based on targeted molecular therapy as opposed to the more traditional approach to cancer therapy," Mischel said.
"This is really going to be the future of cancer research and, in fact, UCLA is a critical player in making that happen," he said.
On average, people who have glioblastoma survive less than a year after the initiation of tumor growth, researchers said.
The proliferation of cancer cells, leading to the brain tumor glioblastoma, is linked to the overexpression of the mutant form of epidermal growth factor receptor, EGFRvIII. Epidermal growth factor receptor (EGFR) is a cell surface protein that is involved in cellular division and cell growth.
The research group studied patients who were treated with drug therapies such as Tarceva and Iressa, which block the signals causing EGFR to become active. The scientists noticed that some patients responded positively to the drug therapies while others did not.
The group found that patients who had both the mutant receptor protein EGFRvIII and the tumor repressor protein, called PTEN, responded more effectively to the drug therapies than patients who did not. Of the patients who underwent drug therapy, the 10 to 20 percent of patients who possessed this molecular signature lived five times longer than the patients who did not. The molecular markers, EGFRvIII and PTEN, were specifically found to be targeted by signal blocker drugs of EGFR.
An independent study of patients at UC San Francisco as well as in brain tissue cells also confirmed the findings.
Treatments for the brain cancer help to extend survival time but there is no cure for the cancer.
"The therapies for glioblastoma patients are not very good. (Using molecular signatures) you can maximize the treatment effect and minimize the unnecessary toxicity," said Maria Wang, a postdoctoral fellow in Mischel´s lab.
Based on molecular signatures, researchers can identify which patients will not respond to signal blockers of EGFR and hence not put these patients through ineffective toxic cancer treatments.
"Nobody has been cured of this (type of cancer) yet. The great thing is that clearly some of the patients benefit from this targeted treatment," said Ingo Mellinghoff, assistant professor in the department of molecular and medical pharmacology.
"This is the first time a highly targeted treatment ... has had substantial impact on the growth of this aggressive tumor," he said.
Further research is being conducted to understand how treatment works.
"(Future research involves) understanding how different components within the tumor will respond to these drugs so we can figure out how to rationally combine drugs to better treat these patients," Mischel said.
The researchers also want to study the patients who didn´t respond to the EGFR signal blocking drugs to determine which therapies are most effective for them.
"We now have a rough idea of what percentage will respond to this treatment and we can select patients who are more likely to respond to it and then understand how we can overcome the ultimate failure of the therapy," Mellinghoff said.
This study can affect the way that cancer therapies are diagnosed to treat patients, using molecular signatures to specifically treat patients, researchers said.
"This helps to begin to figure out how to develop rational or smart combination of drugs to help treat these patients," Mischel said.
Tina[a]
