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![[Divider]](/images/barrule.gif) |
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INNOVATIONS
IN TECHNOLOGIES, TECHNIQUES AND TREATMENTS
FOR BRAIN TUMORS
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A
SURROGATE MEASURING STICK FOR NEW MEDICAL
THERAPIES
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Glioblastoma,
the most common malignant tumor of the brain,
is highly aggressive and usually becomes resistant
to standard treatment over time. “That’s
why it’s so important for patients to
have access to new agents in clinical trials,”
says Batchelor. Among the medical therapies
under investigation for these tumors are drugs
called angiogenesis inhibitors, which are
believed to temporarily normalize leaky blood
vessels supplying the tumor — allowing
chemotherapy and radiation to work more effectively
— and then to block tumor growth. One
of the drugs that has been extensively studied
in the Cancer Center, AZD2171, also known
as cediranib, has shown promising activity
in patients with glioblastoma when other therapies
have failed. (See “Therapeutic Door Opens
for Aggressive Brain Cancer”) |
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Imaging
will also be used at regular intervals to
measure therapeutic effects on the tumor.
All of the half-dozen clinical trials of angiogenesis
inhibitors now in development for brain tumors
at the Cancer Center, says Batchelor, depend
on the advanced imaging techniques of the
Martinos Center. |
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COLD
SORE VIRUSES: UNLIKELY THERAPEUTIC ALLIES
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Although
neurosurgeon Martuza performs image-guided surgery,
he is also known internationally for applying molecular
techniques to problems that surgery cannot solve.
Surgery cannot completely remove glioblastomas,
for example, because malignant cells can infiltrate
the normal tissue surrounding the tumor. So Martuza
and his colleagues pioneered another approach called
oncolytic viral therapy — a close cousin of
gene therapy — in which viruses, such as the
herpes simplex cold sore virus, are genetically
engineered to become cancer-killing agents. |
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In
typical gene therapy, scientists use viruses to
insert a normal or altered gene into cells to replace
a disease causing gene. Viruses are like uninvited
guests that insinuate themselves into a cell’s
environment. Researchers disable the virus so that
it cannot cause infection and use it to slip the
corrective gene inside the cell. Once there, the
virus takes over the cell’s reproduction machinery,
allowing the virus and its healthy gene to replicate. |
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Oncolytic
viral therapy is a variation on this theme. Rather
than engineering the virus to carry a corrective
gene, scientists alter the virus to selectively
replicate in cancer cells but not in normal cells,
explains Martuza. Various manipulation strategies
create viruses that stop the tumor from growing
or kill its newly formed blood vessels. “We
can engineer the herpes virus so that the cancer
cell provides just what the cancer-killing virus
needs to grow within the cancer but not within the
normal tissue.” |
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An
agent called G207 is one of the first clinical applications
of herpes viruses to tumors of the brain. In a clinical
trial in patients with recurrent malignant gliomas
(which include glioblastoma), results were encouraging.
“G207 was safe even at the highest doses, despite
being injected directly into the brain,” says
Martuza. “And in about one-third of patients,
we saw tumor regression on MRI scans.” |
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THE
ONE-TWO PUNCH OF COMBINATION THERAPIES
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In
an effort to improve the efficacy of viral therapy in
malignant gliomas, Curry, Martuza and colleagues are planning
a new clinical trial combining G207 with temozolomide,
an oral chemotherapy drug that works by damaging the DNA
in tumor cells. “When the tumor tries to repair the
DNA,” explains Martuza, “that process actually
stimulates the altered virus to multiply and spread to
other tumor cells, thus killing the tumor.” |
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He
and his colleagues in the Department of Neurosurgery,
Manish Aghi, MD, PhD, and Samuel Rabkin, PhD, recently
demonstrated some striking results using this combination
therapy in mouse models of glioblastoma. Treating with
either temozolomide or G207 alone extended survival from
about 34 days to 50 days. But treating first with temozolomide
and then with G207 — like a one-two punch —
resulted in a 100 percent cure rate. According to Martuza,
combining the therapies is ten times as effective as either
therapy alone. “At least in the preclinical model,
this combination therapy looks very exciting, which is
why we are bringing it into clinical trials.” |
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Others
in the Pappas Center are combining therapies to boost
the efficacy of chemotherapy and radiation. Loeffler,
for example, is studying agents that will enhance the
sensitivity of tumor cells, priming them to become more
susceptible to radiation. Batchelor predicts that these
and other combination therapies on the horizon offer the
greatest hope for improving survival and quality of life
in patients with malignant brain tumors. “We have
already identified critical components of the tumor to
target. Now we need to combine treatments to attack each
of these components.” - Lonnie Christiansen |
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Advancing
the Specialized Care of Individuals with Brain
Tumors
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MGH
Brain Tumor Center
Yawkey Building 9th Floor
Boston, Massachusetts, 02114
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Patients
& Families with questions about referrals, consultations
or appointments may contact:
Telephone: 617.724.8770
Fax: 617.724.8769
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Physicians
with
questions may contact:
Tracy Batchelor, M.D.
Executive Director,
MGH Brain Tumor Center
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| MassGeneral.org |
| MGH
Cancer Center |
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