UAB Comprehensive Cancer Center Magazine Spring 2016 | Page 14
quick takes
RESE ARCH BRIEFS
Ovarian Cancer Survival Rates Do Not
Rise with Paclitaxel
A recent study published in The New England Journal of
Medicine found that administering the cancer drug paclitaxel
weekly versus every three weeks does not prolong progressionfree survival among patients with ovarian cancer.
Paclitaxel, an anti-cancer chemotherapy drug, is commonly
used to treat ovarian, breast, lung, pancreatic and other cancers.
Weekly paclitaxel therapy has been shown to prolong survival
among patients with early-stage breast cancer and those with
metastatic breast cancer, but its effect in ovarian cancer was
unknown.
For this large, multinational study, UAB investigators
looked at the combined dose-dense weekly paclitaxel with
the drug bevacizumab. Overall, results show that a regimen
of weekly paclitaxel did not prolong progression-free survival
(PFS) as compared with a regimen of treatment every three
weeks. Results also indicated patients who did not receive
bevacizumab with a weekly dosage of paclitaxel saw a PFS that
was 3.9 months longer than those receiving paclitaxel every
three weeks.
UAB was a lead enrollment site for this trial, which
involved 692 patients with newly diagnosed, previously
untreated ovarian cancer at more than 209 clinics in the United
States, Canada and South Korea.
New Pathway Sheds Light on Some
Cancers
In humans, the differentiation of stem cells into hundreds
of specialized cell types is vital. Differentiation drives
development from fertilized egg to a newborn, and it underlies
the continuous replacement of the five billion cells that
die every hour in an adult. On the downside, mutations in
differentiation pathways of different cell types can be drivers of
cancers.
Xinyang Zhao, Ph.D., and colleagues Li Zhang,
Ngoc-Tung Tran and Hairui Su at UAB and at seven
other institutions, have discovered a new mechanism of
differentiation, as studied in megakaryocytes, the blood cells
responsible for platelet production.
This mechanism may offer new research and therapeutic
approaches to blood malignancies as well as solid tumors such
as colon and breast cancers. Since two of the key proteins in
the pathway — PRMT1 and RBM15 — are expressed in all
tissues, they may also regulate differentiation in other tissues,
especially those where RBM15 has been shown to be essential
for development, including the heart, spleen and placenta.
The pathway is complex to describe, but its ultimate effect
is an alternative splicing of messenger RNAs — particularly
the messenger RNAs of master regulators called transcription
factors. These factors control the reading of genetic information
from DNA genes and act as switches in all living organisms to
control gene expression.
The work by Dr. Zhao, a Cancer Center associate scientist,
and his colleagues, publis hed online in advance of print in
eLife, has taken four years.
UAB Study Hailed Among Best in Cancer Research
Mona Fouad, M.D., M.P.H.
Research led by Mona Fouad, M.D., M.P.H., director of the UAB Division of Preventive
Medicine, has been selected by the American Society of Clinical Oncology for inclusion in Clinical
Care Advances 2016, the society’s annual review of progress against cancer and emerging trends in
the field. The study, titled “Patient navigation as a model to increase minority participation in cancer
clinical trials,” examines the use of patient navigators for informing and enrolling potentially eligible
African-American patients in clinical trials.
To be successful, cancer clinical trials require participation of individuals from all population
groups. Enrollment and retention are especially challenging among racial and ethnic minorities.
Currently, less than 10 percent of all trial participants are minorities.
For this study, lay individuals who are not medical professionals were hired and trained to serve
as patient navigators. African-American patients potentially eligible for clinical trials were identified
through chart reviews and referrals by clinic nurses, physicians and social workers. The navigators met
with the patients, informed them about current clinical trials, and provided tailored support to those
who decided to enroll in a trial.
Between 2007 and 2014, of 378 African-Americans who were eligible for a clinical trial, 304 enrolled in one and 272 opted to
receive patient navigation support. Among trial participants receiving navigation support, 75 percent completed the trial compared to 38
percent of trial participants not receiving navigation support. The difference in retention rates between the two groups was statistically
significant, and participation of African-Americans in cancer clinical trials increased from 9 percent to 16 percent.
“Although future studies need to evaluate clinical trial participation with other racial and ethnic minorities, this model holds
promise as a strategy to reduce disparities in cancer clinical trial participation,” Dr. Fouad says.
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U A B
C O M P R E H E N S I V E
C A N C E R
C E N T E R
PATIENT AND
FAMILY RESOURCE
CENTER
Promising Leukemia Marker Found
The UAB Comprehensive
Cancer Center’s Patient
& Family Resource Center
provides a comfortable
place to find support. If you
or a loved one has been
diagnosed with cancer,
our staff can answer your
questions about the illness,
treatment options and
available support services.
UAB researchers have found a marker on blood cells that may help
the most pressing problem in chronic myelogenous leukemia (CML)
today — an inability to get patients off treatment.
“To do that, we have to be able to maintain their remission after
stopping treatment,” says Ravi Bhatia, M.D., director of the UAB
Division of Hematology-Oncology and Cancer Center deputy director.
“Treatment using drugs called tyrosine kinase inhibitors, or TKIs, do
not eliminate leukemia-initiating cells.”
In most patients, residual leukemia-initiating cells result in
Ravi Bhatia, M.D.
regeneration of leukemia, necessitating lifelong treatment with
these drugs. Only a small proportion of CML patients stay in remission after stopping TKI
treatment. Two keys to containing remission may be the ability to identify those patients who
will be able to successfully stop their TKI without later relapse and, second, the ability to
identify patients who may benefit from an additional drug regimen besides TKI to achieve
treatment-free remission.
Research by Dr. Bhatia and colleagues, published in The Journal of Clinical Investigation,
shows that the leukemia-initiating stem cells in the bone marrow are not uniform. Instead,
evidence points to a mixed population of cells that can be distinguished by several cell markers,
significantly Mpl gene expression. Cells with high Mpl gene expression are prone to initiating
the disease-causing profusion of white blood cells in animal models of CML.
Over the past 15 years, CML has had a marked improvement in five-year survival thanks
to TKI drugs, from about 30 percent to nearly 90 percent today. However, the drugs have to be
taken every day for a patient’s lifetime, and their yearly cost can be $100,000 to $150,000. This
is a societal burden, and for some patients the drug co-payments can exceed their ability to pay.
Identifying those who could safely stop TKI treatment would be a boon to patients and society.
This can include:
n Cancer Prevention
n Dealing with Side Effects
n Clinical Trials
n Complementary Therapies
n Stress Management
n Spirituality
UAB Researchers Identify Key Protein in Brain Cancer
n Support Groups & Oneon-One Support
A team of UAB physicians and scientists recently discovered that a kinase protein known as
MLK4 plays a crucial role in survival of patient-derived brain cancer stem cells in pre-clinical
animal models. These findings suggest that MLK4 could potentially be a useful target for
cancer treatment.
Protein kinases are key regulators of cell function that constitute one of the largest and
most functionally diverse gene families. Until recently, MLK4 was considered a poorly
characterized kinase. The UAB team, however, identified this gene from a stepwise screening
of molecules that are elevated in cancer stem cells isolated from brain cancer patients.
The findings, published in Cancer Cell, nailed down the novel molecular mechanisms for
which MLK4 is essential in cancer stem cells and not in normal cells in the human body. Most
importantly, brain cancer patients with higher MLK4 expression have shorter survival despite
the current intensive therapies including surgery, chemotherapy and radiotherapy. Nonetheless,
there are no MLK4-targeting therapies or clinical trials currently available for patients.
“There is no doubt that society desperately needs new and effective therapies for this lifethreatening brain disease. Improvement of patient survival for the past 50 years has been
counted by months and not years,” says Ichiro Nakano, M.D., Ph.D., professor in the UAB
Department of Neurosurgery and principal investigator of the study. “We, as an international
collaborative team centered at UAB, focus on cancer stem cells as a therapeutic target in brain
cancers.”
Collaborative participants on this project include M.D. Anderson, Ohio State University,
University of Texas, Northwestern University, Cincinnati Hospital Medical Center, and a
variety of German and Japanese research departments and institutes. The work was supported
by the American Cancer Society, the Grant-in-Aid for Scientific Research from the Japan
Society for the Promotion of Science and Takeda Science Foundation.
# K N O W U A B C C C
n Mindful Meditation
n Restorative Yoga
n Art Therapy
PATIENT & FAMILY
RESOURCE CENTER
Wallace Tumor Institute,
Room 220
For more information, contact
Teri Hoenemeyer,
(205) 934-5772
[email protected]
•
U A B . E D U / C A N C E R
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