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.