a cancer biologist and neuropathologist at the
Ludwig Institute for Cancer Research in San Diego.
Molecular biomarkers can help predict a brain
tumor’s likely response to the chemotherapy drug
Temodar. This testing can also help assess the risk
that a tumor will grow and spread, and can reveal
certain genetic variants in the tumor that may
respond to experimental treatments. However,
genomic testing of brain tumors has yet to uncover
ways to extend survival beyond that provided by
Why the Head Is So Hard
More than 80,000 people in the U.S. are diagnosed
with some type of brain tumor each year; of those
tumors, about a third are malignant. Brain tumors
are usually diagnosed following the onset of troubling symptoms, such as seizures, nausea, vomiting,
drowsiness or memory problems.
Astrocytoma, Salmi’s tumor type, is a glioma. The
most common type of brain cancer, gliomas originate in glial cells, which surround neurons in the
brain. Gliomas are graded from I to IV. The most
aggressive type is grade IV, called glioblastoma,
which has the worst prognosis. The median survival
after a glioblastoma diagnosis is around 15 months, a
number that has barely budged in the past 50 years.
Compared to treatment advances for other types
of cancer, progress in treating brain cancer has
been frustratingly slow. The U.S. Food and Drug
Administration (FDA) has approved 16 targeted
therapies for lung cancer, 15 for breast cancer
and seven for colon cancer, but only one—Avastin
(bevacizumab)—for malignant brain tumors. And
there’s no evidence that Avastin extends survival
longer than chemotherapy and radiation, though it
may delay symptoms and extend the time it takes for
a tumor to grow.
Targeted drugs and immunotherapies that have
generated excitement by extending survival in
some patients with other cancer types have largely
failed in clinical trials for brain cancer patients.
“Brain tumors do not respond to a lot of the treatment strategies that we try to impose on them,”
says Eric T. Wong, a neuro-oncologist at Beth Israel
Deaconess Medical Center in Boston.
There are a number of reasons for this, he says.
First, heterogeneity: Brain cancer tumors contain
a staggering mix of cells with different mutations,
not only from person to person but within a single
tumor. That means a treatment that targets one type
of mutation might be ineffective against cells in the
tumor with a different set of mutations. A treatment-resistant tumor could be the result. “The cells that
are most likely to be resistant are the ones most
likely to thrive,” says Mischel.
Then there’s the hurdle of location. Even though
brain cancer rarely spreads to other parts of the body,
brain tumors such as gliomas can extend like tendrils
into surrounding brain tissue. Thus, even the best
surgical resections can’t remove all the cancerous
cells from the delicate tissue of the brain.
In addition, “the barrier to the brain is tightly
controlled,” says Mischel. This blood-brain barrier,
which blocks foreign substances in the blood
from entering the brain, can also impede cancer
Molecular analysis offers one way to rethink
clinical trials and to help identify patients
who might benefit from a given drug.