HITTING THE MARK
Targeted Agent Shows Promise in Biliary Cancer
The experimental agent selumetinib
showed promising results in people
with advanced biliary cancer in a
multi-institutional study led by researchers
at The Ohio State University
Comprehensive Cancer Center – James
Cancer Hospital and Solove Research
Institute (OSUCCC – James).
Findings from this 28-patient phase
II study indicate that selumetinib, also
known as AZD6244 (ARRY-142886),
inhibits the MEK protein, which cancer
cells need to proliferate and survive.
The tumor shrank to an undetectable
level in one patient, and
two patients showed partial tumor
shrinkage. In 17 patients, the tumor
stopped growing for up to 16 weeks
in most cases. On average, patients
experienced no cancer progression
for a promising 3.7 months, even
though nearly 40 percent had prior
therapy (such tumors tend to resist
"Biliary cancer has no good
standard of care," says principal investigator
Tanios Bekaii-Saab, MD,
medical director of gastrointestinal
oncology at the OSUCCC – James.
He notes that most patients present
at later stages of the disease, which
has a universally poor outcome.
"Our study provides a strong rationale
for developing this agent further
in larger trials, which we hope
will enable us to establish a new
standard of care."
Bekaii-Saab says patients who
lacked a target protein called pERK
did not seem to respond to the drug.
"This suggests that we may be able to
identify which patients are most likely
to benefit from this agent," he adds.
Published in the Journal of Clinical Oncology.
Novel Drug Highly Active in CLL Patients
An interim analysis of a phase II
clinical trial indicates that an experimental
agent for chronic lymphocytic
leukemia (CLL) is highly
active and well tolerated both in
previously treated patients and in
those who have relapsed and are
resistant to other therapy.
The agent, PCI-32765, is the
first drug designed to target Bruton’s tyrosine kinase, a molecule
essential for CLL-cell survival and
Study leader John C. Byrd, MD,
director of the Division of Hematology
at Ohio State, presented the findings at the 2011 American Society
of Clinical Oncology (ASCO)
annual meeting in Chicago.
The trial involves 78 patients with
previously untreated or relapsed
and refractory CLL or small lymphocytic
leukemia. This analysis
involved the first 21 cases in the
untreated-patient group and the
first 27 individuals in the relapsed/
refractory-patient group. One patient
in each group had a complete
remission, while 13 patients in the
previously untreated group and 12
patients in the relapsed group had
"These are early findings, so patients
with partial remissions could
improve to complete remissions with
further observation," Byrd says.
Amy Johnson, PhD, co-led
pre-clinical CLL work on PCI-
32765 at Ohio State, along with
Byrd. Those findings, published in
the journal Blood, showed that the
agent targets B lymphocytes and
spares T lymphocytes. If the agent
behaves the same way in humans,
"It could dramatically improve outcomes
for CLL patients," Byrd says.
microRNA Findings May Lead to Blood Test for Lung Cancer
OSUCCC – James researchers have identified characteristic patterns of microRNA molecules (miRNA) in the blood of lung cancer patients that might reveal the presence and aggressiveness of the disease, and perhaps who is at risk of developing it.
These patterns may be detectable up to two years before the tumor is found by computed tomography (CT) scans. The findings could lead to a blood test for lung cancer, according to principal investigator Carlo Croce, MD, director of the Human Cancer Genetics Program at Ohio State.
Croce and his collaborators identified the molecular patterns in tissue and blood samples collected from patients participating in a clinical trial examining the use of spiral CT scans to screen for lung cancer. The trial involved 1,035 individuals aged 50 years or older who had smoked at least a pack of cigarettes a day for 20 years or more.
"It might be possible to use these patterns of abnormal microRNAs in the plasma to detect lung cancer in people with the disease," Croce says. "The abnormal microRNAs were also present in blood serum well before the tumors were detected by a sensitive method such as spiral CT scan, suggesting the possibility of identifying high-risk patients on the basis of miRNA profiling."
Published in the journal Proceedings of the National Academy of Sciences.
Low-Dose Sorafenib May Improve Therapy for Head and Neck Cancer
Adding low doses of the targeted agent sorafenib to the chemotherapy and radiation now often used to treat head and neck cancer might significantly improve patient care and quality of life, a preclinical study at the OSUCCC – James suggests.
The findings indicate that adding sorafenib would maintain treatment efficacy while permitting lower doses of chemotherapy and radiation, thus decreasing harsh side effects. The triple combination was well-tolerated in an animal model.
About 49,200 new cases of head and neck cancer are expected in the United States this year, and 11,500 people are expected to die from it. Treatment is often unsuccessful because the tumors become resistant to both chemotherapy and radiation therapy.
"This preclinical study suggests that using low-dose sorafenib plus chemotherapy and radiation could have significantly milder side effects while maintaining effectiveness," says principal investigator Pawan Kumar, PhD. "Our findings provide a scientific rationale to evaluate this combination strategy through a clinical trial."
"Our results suggest a potentially novel strategy in which sorafenib combined with low doses of chemotherapy, radiation therapy or both is as effective in treating head and neck cancer as much higher doses used in existing treatment," says study co-author Theodoros Teknos, MD, who directs the Division of Head and Neck Surgery at Ohio State.
Published in the journal Molecular Cancer Therapeutics.
Gene Change Signifies Better Response to Treatment
Arnab chakravarti, MD, Chair and professor of Radiation Oncology, co-director of the Brain Tumor Program, member of the Experimental Therapeutics Program and the Max Morehouse Chair in Cancer Researchn.
New research proves that a change in the MGMT gene can identify which patients with glioblastoma will respond better to treatment. Testing for this gene can distinguish patients with a more- or less-aggressive form of this disease – the most common and deadliest type of primary brain cancer – and help guide therapy.
Examining the MGMT gene in tumors removed from 833 patients with glioblastoma, the researchers found that when the gene promoter is altered by a chemical change called methylation, patients respond better to treatment.
"We show that MGMT methylation represents a new genetic test that can predict clinical outcomes in glioblastoma patients treated with radiation combined with the chemotherapeutic drug temozolomide," says co-author Arnab Chakravarti, MD, chair of Radiation Oncology and co-director of the Brain Tumor Program at the OSUCCC – James.
"Glioblastomas are a collection of different molecular and genetic entities that behave uniquely and require personalized treatment," adds Chakravarti, who is the translational-research study chair for the study.
The findings were presented in June at the 2011 American Society of Clinical Oncology (ASCO) meeting.
To refer a patient, please call The James Line New Patient Referral Center toll free: 1-800-293-5066.
Component of Chinese Herbal Remedy Might Block Brain Tumor's Spread
E. Antonio Chiocca, MD, PhD professor and chair of Neurological Surgery, Dardinger Family Endowed Chair in Oncological Neurosurgery and co-leader of the OSUCCC – James Viral Oncology Program
The active ingredient in a traditional Chinese herbal remedy might help treat deadly brain tumors, according to a study by OSUCCC – James researchers.
The laboratory and animal study suggests that a substance called indirubin blocks both the migration of glioblastoma cells, preventing their spread to other areas of the brain, and the migration of endothelial cells, inhibiting the formation of tumor blood vessels.
"We have pretty good methods to stop glioblastoma from growing in the human brain, but these therapies fail because tumor cells migrate from the original site and grow elsewhere in the brain," says co-principal investigator E. Antonio Chiocca, MD, PhD, professor and chair of neurological surgery and co-leader of the OSUCCC – James Viral Oncology Program.
"Our findings suggest that indirubins offer a novel therapeutic strategy for these tumors that simultaneously targets tumor invasion and angiogenesis," he says.
Indirubin is derived from the indigo plant. It is the active ingredient in the Chinese herbal remedy called Dang Gui Long Hui Wan, which is used to treat chronic myeloid leukemia. However, little is known about the form or dose used, or its effectiveness, side effects or drug interactions.
"Although indirubin looks promising in animal models, it has not yet been tested in humans, and it is not approved by the U.S. Food and Drug Administration," Chiocca cautions.
For other work on glioblastoma cell motility by Chiocca, see Researchers Discover Brain Tumor's "Grow-or-Go” Switch.
Published in the journal Cancer Research.
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