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By E. Kevin Hrusovsky, PerkinElmer Inc. As the complexity and volume of data continue to rise, bioinformatics is emerging as one of the cornerstones of personalized medicine, from enabling discovery and development of novel treatments and diagnostics to facilitating collection, analysis and interpretation of data that ultimately helps an individual patient. SPECIAL REPORT PART 1: ‘Good enough’ is no longer good enough By Randall Willis, ddn Features Editor Aiming beyond the standard of care in oncology By Randall Willis, ddn Features Editor Are we really making things better for cancer patients? High-profile oncology partnership By Jim Cirigliano, ddn Contributing Editor Araxes Pharma and Janssen Biotech ink oncology drug development deal Natural neighbors By Kelsey Kaustinen, ddn Features Editor OSU, Biosortia link up to identify natural products for potential cancer treatments  |
 Sunshine State collaboration
March 2012
SHARING OPTIONS:
According to Dr. John Reed, CEO of Sanford-Burnham, the
ultimate goal of the partnership is to conduct collaborative research to
accelerate biomarker and target discovery with an initial focus on developing
new personalized treatments in the areas of cancer and also metabolic diseases,
including obesity, diabetes and cardiovascular disease.
Reed adds that the parties believe there is significant
opportunity to create synergies between the research and clinical care
organizations to advance scientific discoveries and translation of
compassionate care, cures and prevention of disease.
Des Cummings, executive partner of Florida Hospital,
explains that each of the three partners came to the table with a culture of
innovation and each is motivated to creatively solve the toughest medical care
problems that exist today.
“The field of medicine is on the brink of transformation
based on next-gen DNA sequencing and other technologies that enable biomarker
discovery,” Reed says. “We believe that the partnership with Moffitt, Sanford-Burnham
and Florida Hospital provides the infrastructure to create personalized
treatment plans based on biomarker discovery technology platforms. We seek to
identify molecular signatures that dissect disease heterogeneity into different
treatment strategies that improve healthcare outcomes while ideally also
reducing healthcare costs.”
Collaborations between research and clinical organizations
are increasing as a means to access complementary resources, attract more
sizable grant revenues and enhance the translation of laboratory research to
clinical application.
“I believe that it is becoming more and more widely accepted
that we are on the cusp of a new era of medicine with the opportunities that
are being made available to us,” Reed says. “We have opportunities through
next-gen DNA sequencing on one hand, and on the other hand, the challenges
around healthcare costs and how we can eventually evolve the practice of
medicine to something more of a science and less of an art—and get more of the
trial and error out of it and make it more efficient in terms of healthcare
delivery.”
“This is an incredible opportunity for the three to come
together and capitalize on our strengths to create a better product, which is
information,” he says.
According to Dalton, Total Cancer Care is a treatment path
that begins by mapping the more than 30,000 genes that make up a tumor to find
its own unique genetic fingerprint. Through personalized medicine, Moffitt is
working to create individualized therapies that are specific to each patient’s
type of cancer, and the way each person responds to the disease and treatment
therapies.
PMP Florida will provide researchers at the partnering
institutions with access a robust research and clinical care infrastructure.
Bio-samples representing a variety of diseases will be derived from Florida
Hospital’s expansive patient population. Pilot projects will utilize Moffitt’s
genome mapping, information systems and clinical research protocols developed
through Total Cancer Care. The research will be empowered by Sanford-Burnham’s
scientific expertise in genomics and metabolics technology platforms.
A business development plan will be created with input from
representatives of the three partnering organizations. A steering committee
will prioritize research projects.
As for funding, Reed notes that each organization will bear
its own costs and expenses for its respective activities in connection with the
development and execution of the partnership. The initial phase of this
relationship will focus on collaboration efforts for care and research between
researchers and physicians at Moffitt, Sanford-Burnham and Florida Hospital.
Reed adds that the partners will emphasize short-term “wins” and milestones,
which will include research and joint publications.
“Important milestones will be the development of our first
clinic/hospital ready biomarker, external industry partnerships which
capitalize on the PMP infrastructure and ultimately, improvements in the
quality and healthcare cost reductions,” Cummings says. “Ultimately, the
success of the partnership will be based on the ability to improve diagnosis,
treatment, and prevention of disease. This is a journey that is worthy of our
best efforts, and is fueled by our common commitment to advance the health and well-being
of all humanity.”
The laboratory of Dr. Ze’ev Ronai has been studying a
protein named Activating Transcription Factor 2 (ATF2), which is associated
with poor prognosis in melanoma. ATF2 is oncogenic in melanoma ells and acts as
a tumor suppressor in non-malignant types of skin cancers. In a paper published
Feb. 3 in the journal Cell, the team
identified a molecular switch that controls ATF2’s dual functions. This switch
is controlled by protein kinase Cε (PKCε), which disables ATF2’s
tumor-suppressing activities, sensitizing cells to chemotherapy; instead,
ATF2’s tumor-promoting activity is enhanced. The team also found that high
levels of PKCε in melanoma are associated with poor prognosis.
In the study, Ronai and lead author Dr. Eric Lau found that
PKCε’s malignant power is in its ability to direct ATF2’s location and activity
within a cell. In a normal cell, PKCε modifies ATF2, keeping it in the nucleus,
where it turns genes on and off and helps repair damaged DNA. When the cell
experiences exposure to toxicity or stress, PKCε backs off and ATF2 is able to
move out of the nucleus and to the mitochondria, the part of the cell that
generates energy and helps control cellular life and death. When it gets there,
ATF2 helps to set the cell on a death course—a safeguard cells use to prevent
errors that often make them cancerous.
PKCε levels are abnormally high in melanoma, and more PKCε
means more ATF2 stuck in the nucleus, where it can't help the cells to die.
Instead, in the nucleus, ATF2 promotes cellular survival and thus contributes
to tumor development.
The researchers are now searching for small molecules that
help release ATF2 from PKCε’s grip, thereby resuming ATF2’s ability to promote
cell death when needed. Since such an approach will effectively kill melanoma
cells, it is expected to offer new therapeutic options for melanoma and
possibly other tumors with high PKCε levels.
“This work has clear potential for translation from a basic
laboratory discovery to a melanoma therapy,” said Dr. Michael Jackson, vice
president of drug discovery and development at Sanford-Burnham, in a statement.
“We are excited to begin the screening process to identify a new class of drugs
to treat cancer.”
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