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- Posted Friday May 1, 2015
TGen-UCSF study published in Neuro-Oncology provides comprehensive look at brain cancer treatments
New clinical trial at UCSF, based on TGen genomic research, uses multiple drugs to cross blood-brain barrier and attack glioblastoma tumors
PHOENIX and SAN FRANCISCO - May 1, 2015 - Led
by the Translational Genomics Research Institute (TGen)
and UC San Francisco (UCSF), a comprehensive genetic review of
treatment strategies for glioblastoma brain tumors was published
today in the Oxford University Press journal
Neuro-Oncology.
The study, Towards Precision Medicine in Glioblastoma: The
Promise and The Challenges, covers how these highly invasive
and almost-always-deadly brain cancers may be treated, reviews the
continuing challenges faced by researchers and clinicians, and
presents the hope for better treatments by harnessing the power of
the human genome.
The study also describes a pioneering clinical trial underway for
15 patients at UCSF, guided by TGen research, in which an
individual patient's genomic profile is used to offer treatment
recommendations to an expert, multidisciplinary panel.
"This study thoroughly explores how we arrived at the current
standard-of-care, and how - through cutting-edge genomic
technologies - we might find better answers for these patients who
need our help today," said Dr. Jeffrey Trent, TGen President and
Research Director and the study's senior author.
Funded by The Ben & Catherine Ivy Foundation, the study is one
of several simultaneous and coordinated efforts seeking to uncover
the molecular source of this deadly brain cancer with the goal of
prolonging survival of glioblastoma patients.
"Despite pivotal advances in the characterization of genomic
mutation in glioblastoma, targeted drug agents have so far shown
minimal effect in clinical trials, and patient survival remains
poor," said Dr. Michael D. Prados, the Charles B. Wilson, MD,
Endowed Chair in Neurological Surgery at UCSF, and one of the
study's co-lead authors.
One of the major difficulties in treating brain tumors is finding
drugs that can penetrate the blood-brain barrier, which buffers the
brain from the rest of the body's blood-circulatory system. Located
along capillaries, the blood-brain barrier protects the brain from
rapid changes in the body's metabolic conditions and minimizes
exposure to molecules that are toxic to neurons in the brain.
"This study outlines strategies for overcoming past failures,
primarily by applying targeted combination therapies that match the
tumors' genetic changes with drug compounds that can reach the
central nervous system," said Dr. Sara Byron, Research Assistant
Professor in TGen's Center for Translational Innovation, and the
study's other co-lead author.
Another major challenge in treating glioblastoma is its intrusive
penetration into adjoining tissues, which prevents the complete
surgical removal of the tumors from the brain, even with follow-up
radiation and chemotherapy: "It is this invasive, infiltrative
disease component that is the ultimate cause of recurrence,
resistance and death," the study says.
"All patients will continue to show tumor growth and progression
because of rapidly proliferating infiltrative disease remaining
after surgery," according to the study. "Effective treatment for
glioblastoma remains an unmet need."
The only FDA-approved drugs to treat glioblastoma are
temozolomide, nitrosoureas, and bevacizumab.
In the clinical trial begun at UCSF, multiple biopsies are
performed on each patient at the time of surgery in different
regions of the brain tumor. That is followed by extensive
genome-wide profiling, leading to a selection of drugs that would
target the brain cancer and diffuse regions of the lesion that
cannot be removed by surgery.
Drug selection is individualized, and multiple FDA-approved agents
(up to four) allowed. "Rules" for drug selection are implemented,
using the specialized drug pharmacopeia designed for this trial.
The drugs are chosen carefully, considered with knowledge about the
ability of the drug to reach the brain and the patient's past
treatment history and concomitant therapies, with the assistance of
multi-specialty, multi-institutional molecular tumor board that
drafts a report to the treating physician.
In addition, "Small, informative, tissue-based clinical trials
that take into account the individual molecular features of
patients and provide early 'go' or 'no go' decisions are needed and
should be prioritized over unselected, large, population-based
strategies," the study recommends.
A separate clinical trial that follows this path, also guided by
TGen genomic research, is underway at Barrow Neurological
Institute. This clinical trial also is funded by The Ben &
Catherine Ivy Foundation. For more about this clinical trial, go
to: www.tgen.org/home/news and click
on March 10, 2015.
"These studies, and their associated clinical trials, have the
potential to lift our knowledge of glioblastoma to an unprecedented
new level," said Catherine Ivy, President of The Ben &
Catherine Ivy Foundation. "Developing drug compounds that breach
the blood-brain barrier and are effective against tumors would
fulfill one of the medical community's most critical unmet needs,
and boost the hopes of brain tumor patients everywhere."
Contributing to the study published today were all three TGen
Deputy Directors: Dr. John Carpten, Deputy Director of Basic
Science; Dr. Michael Berens, Deputy Director for Research
Resources; and Dr. David Craig, Deputy Director of
Bioinformatics.
# # #
About UC San Francisco
UCSF is the nation's leading university exclusively focused on
health. Now celebrating the 150th anniversary of its founding as a
medical college, UCSF is dedicated to transforming health worldwide
through advanced biomedical research, graduate-level education in
the life sciences and health professions, and excellence in patient
care. It includes top-ranked graduate schools of dentistry,
medicine, nursing and pharmacy; a graduate division with
world-renowned programs in the biological sciences, a preeminent
biomedical research enterprise and top-tier hospitals, UCSF Medical
Center and UCSF Benioff Children's Hospitals. Please visit www.ucsf.edu.
About TGen
Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. TGen is focused
on helping patients with cancer, neurological disorders and
diabetes, through cutting edge translational research (the process
of rapidly moving research towards patient benefit). TGen
physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children.
Working with collaborators in the scientific and medical
communities literally worldwide, TGen makes a substantial
contribution to help our patients through efficiency and
effectiveness of the translational process. For more information,
visit:www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
About The Ben & Catherine Ivy
Foundation
The Ben & Catherine Ivy Foundation, based in Scottsdale,
Ariz., was formed in 2005, when Ben Ivy lost his battle with
glioblastoma multiforme (GBM). Since then, the Foundation has
contributed more than $50 million to research in gliomas within the
United States and Canada, with the goal of better diagnostics and
treatments that offer long-term survival and a high quality of life
for patients with brain tumors. The Ben & Catherine Ivy
Foundation is the largest privately funded foundation of its kind
in the United States. For more information, visit www.ivyfoundation.org.
About Neuro-Oncology
Neuro-Oncology, published by Oxford University Press, is
the leading journal in the field, dedicated to providing superior
and rapid publication of information in all areas of
neuro-oncology. The journal contains peer-reviewed articles and
reviews, symposia on selected topics, published abstracts of annual
meetings, and society news and announcements from around the
world.