Prostate Cancer Foundation Awards $3.6 Million in 12 New Creativity Awards for Advanced Research

Wed May 12, 2010 9:00am EDT

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Innovative Projects are Selected for their Potential to Accelerate Discovery and
Deliver Game-Changing Results for Prostate Cancer
SANTA MONICA, Calif.--(Business Wire)--
The Prostate Cancer Foundation (PCF) today announced that it has funded twelve
new Creativity Awards to support innovative projects because of their potential
to fast-forward discovery and deliver game-changing results for prostate cancer
research. These two-year awards are designed to support new ideas that may lead
to the development of better diagnostics, new treatments and even cures for
prostate cancer. The type of research ideas encouraged by PCF`s Creativity
Awards are typically not funded by any existing government or other private
sources. 

"We continue to lose an American man to prostate cancer every 19 minutes and
more than 192,000 new cases will be diagnosed this year," said Howard Soule,
PhD, executive vice president and chief scientist for PCF. "New approaches for
treating this disease are urgently needed. The talent and creative thinking of
these 12 award recipients will feed our discovery pipeline and cultivate new
solutions for the prostate cancer." 

A rigorous peer review process vetted the 12 selected projects from a field of
more than 157 applications representing 92 institutions in 11 countries.
Historically, 70 percent of such PCF awards have gone on to attract additional
multi-year funding from PCF and other sources. 

"Seven of these new Creativity Awards fund entirely new classes of
anti-prostate-cancer medicines that have never before entered clinics,"
commented Jonathan W. Simons, MD, president and CEO of PCF. "With these awards,
we are replenishing our pipeline of potentially promising new treatments for
patients." 

2010 PCF Creativity Awards

Gustavo Ayala, MD
Baylor College of Medicine, Texas

Targeting Neurogenesis in Prostate Cancer

The prostate gland is rich in nerves and proteins that support nerve growth
(neural growth factors). Studies from Dr. Ayala`s group have demonstrated that
prostate cancer cells directly interact with nerves. The data also showed that
nerve density in the prostate was highest in areas with cancer. Based on these
observations, Dr. Ayala hypothesized that neurogenesis (nerve growth) permits
and/or promotes prostate cancer progression. To test this, Dr. Ayala and
colleagues have designed a first-in-man clinical trial testing a powerful
neurotoxin, Botulinum Neurotoxin Type A (BoNT-A) also known as BOTOX, that
blocks nerve activity and growth. This study will determine whether interruption
of neurogenesis with BoNT-A activates anti-tumor activity and will identify the
tumor-promoting mechanism underlying the interaction between nerve cells and
prostate cancer cells. 

Brendan Curti, MD
Providence Portland Medical Center, Oregon

Augmenting OX40 Immunotherapy in Men with Advanced Prostate Cancer

Dr. Curti and his team are pioneers in the preclinical and clinical development
of a new immunotherapy that activates the anti-tumor effects of patients` own T
cells (a type of white blood immune cell). This new target, OX40, is a cell
surface molecule on T cells that when properly activated can induce T cells to
kill cancer cells. A Phase I Clinical Trial showed that prostate cancer patients
treated with a monoclonal antibody directed against OX-40 (anti-OX40) had the
greatest increase in the frequency of anti-tumor T cells relative to other solid
tumor patients. Additionally, pre-clinical studies in mouse models revealed that
anti-OX40 in combination with chemotherapy and radiation had the greatest
anti-cancer effect. This project will extend these findings into the clinic by
initiating a clinical investigation to evaluate anti-OX40 in combination with
chemotherapy and radiation therapy in patients with metastatic prostate cancer.
During the study, the investigators will be monitoring the frequency of T cells
in patients undergoing treatment to identify whether T cell quantification can
predict clinical response to this treatment strategy. Anti-OX40 is first-in-man,
first in prostate cancer. This work promises to enhance effectiveness of
immunotherapy. 

Jennifer Doll, PhD
NorthShore University HealthSystem Research Institute, Illinois

Periprostatic Fat as a Promoter of Prostate Cancer Progression

Obesity and high fat diets are associated with more aggressive prostate cancer.
Yet, the mechanism underlying this association remains unclear. Dr. Doll and
colleagues hypothesize that periprostatic fat (fat adjacent to the prostate)
from obese patients has an enhanced capacity to promote prostate cancer growth
by increasing the level of triglycerides and fatty acids within cancer cells.
Fatty acids and triglycerides have been shown to promote prostate cancer cell
growth in vitro and analysis of obese patient tumor specimens revealed that many
cancer cells contained fat droplets. In her proposal she plans to identify how
fatty acids and triglycerides released from periprostatic fat promote prostate
tumor growth and whether levels of fatty acid and triglycerides in the
periprostatic fat correlate with clinical outcome. Early data from Dr. Doll`s
work reveal that fat may block the production of an important protein called,
PEDF. PEDF suppresses fatty acid and triglyceride accumulation and blocks new
vessel growth called angiogenesis in the tumor. This study may identify new
therapeutic targets, such as PEDF, for the treatment of advanced prostate
cancer. 

The Evensen Family - PCF Creativity Award

Charles Drake, MD, PhD
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Maryland

Combining PD-1 Mediated Checkpoint Blockade with Active Immunotherapy for
Prostate Cancer: A Neoadjuvant Trial

The immune system is capable of identifying cancer cells as foreign and causing
their destruction. This decades-old theory is called immune surveillance.
However, in many patients, including men with prostate cancer, the immune system
becomes fatigued and can no longer prevent cancer progression. PD-1 is a cell
surface protein that is expressed on exhausted immune cells and impairs an
anti-tumor immune response. Dr. Drake has designed a comprehensive study to
assess the clinical value of combining immunotherapy (a cancer vaccine) with an
inhibitor of PD-1 to enhance a patient`s immune response against advanced
prostate cancer. Blockade of PD-1 releases the brakes on the immune response,
revitalizing the body`s ability to kill cancer cells. Anti-PD1 is in
first-in-man clinical testing. This project could enhance the efficacy of
immunotherapy treatments in men with advanced prostate cancer. 

James Marshall, PhD
Roswell Park Cancer Institute, New York

Diet and Progression of Prostate Cancer among Men on Active Surveillance

Active surveillance is a clinical program for men diagnosed with very early (low
grade and stage) prostate cancer who decide with their physician to delay
treatment. The challenge during active surveillance is to prevent disease
progression and the subsequent need for local therapy. Extensive epidemiological
studies suggest that metabolic changes from a calorie-controlled diet high in
fruits and vegetables are associated with reduction in risk for prostate cancer
progression. Dr. Marshall proposes to test these observations in a clinical
study called Men`s Eating and Living (MEAL) study, a rigorous dietary
intervention. Men will change their diet to the following: 7 servings per day of
vegetables (2 cruciferous, 2 tomato products, 3 other vegetables), 2 servings
per day of whole grains, 1 serving per day of beans or other legumes, and 2
servings per day of fruit. Over a 2 year period, study participants will be
closely monitored for metabolic changes by measuring the chemical byproducts
released from cells into circulation. The results from this study will define
the impact of a dietary intervention on delaying surgical or radiation treatment
in this subset of patients. The study will also identify molecular correlates of
dietary change which may provide insight into novel prostate cancer therapeutics
and/or cancer prevention strategies. 

Nora Navone, MD, PhD
University of Texas M. D. Anderson Cancer Center

FGFR Inhibition to Develop Effective Combination Therapies

Fibroblast growth factor (FGF) and its receptor (FGFR) form a protein-protein
complex that has been implicated in prostate tumor cells as a pathway that
drives prostate cancer progression and metastasis. FGF signaling causes blood
vessel growth within the tumor through a process called angiogenesis. This
process provides the growing tumor with nourishing blood and drives tumor cell
growth. Dr. Navone and colleagues have initiated a first-in-man clinical study
to assess the effectiveness of a novel agent called TKI258, an inhibitor of FGF
signaling. The study includes a comprehensive molecular profiling of patient
tissue obtained from metastatic sites. Results will inform how prostate cancer
cells respond to TKI258 at the molecular level. These findings will advance our
understanding of tumor progression and metastasis and may credential TKI258 as a
new therapy for advanced prostate cancer. 

William Oh, MD
Mount Sinai School of Medicine, New York

Predicting Response to Platinum Chemotherapy in Metastatic Castration-Resistant
Prostate Cancer (CRPC) Using a Genomic Signature for "BRCAness"

Every cell has DNA repair mechanisms that function to protect DNA from harmful
mutations which can cause cancer and cell death. In healthy cells DNA repair
mechanisms are intact but in cancer cells they are often but not always damaged.
Platinums are a class of chemotherapy medicines that kill cancer cells by
damaging the cell`s DNA structure. However, certain types of cancer cells are
more susceptible to DNA-damaging drugs like platinum than others. Satraplatin is
a type of platinum that is unique; it can cause more severe DNA damage than its
counterparts. Yet, BRCA1 and BRCA2 are two genes that may predict satraplatin
activity and confer therapy sensitivity. Importantly some patients carry BRCA1
and BRCA2 mutations resulting in limited DNA repair function. Dr. Oh
hypothesizes that patients with loss of BRCA1/2 function will benefit more from
satraplatin therapy-particularly if the cancer is anaplastic-because the cancer
cells lack the ability to repair themselves. This award will fund a prospective
Phase II clinical trial of satraplatin in metastatic prostate cancer patients
that will determine whether patients with mutated BRCA1 and BRCA2 genes are more
sensitive to satraplatin therapy. Such findings will advance personalized
medicine in prostate cancer treatment strategies and can be applied to newer
drugs that also target this DNA repair pathway. 

Renata Pasqualini, PhD
University of Texas M. D. Anderson Cancer Center

Implications of Obesity in Prostate Cancer Recurrence and Progression- A Novel
Fat-ablating Strategy to Overcome the Cancer Promoting Effects of Obesity

Obese men are more likely to develop aggressive prostate cancer and to
experience disease recurrence than normal weight men. The significant level of
adipose tissue (fat) in obese men has therefore been implicated as a critical
contributing factor in poor prostate cancer outcome. Adipose tissue can be
categorized into two different types: white fat and brown fat. White fat has
been identified as the "bad" fat for cancer, and is most abundant in obese men.
Prohibitin-TP01 is a new agent, discovered in Dr. Pasqualini`s lab, which
specifically targets the vasculature that nourishes white fat. Preclinical
studies in mouse models showed that TP01 treatment reduced white fat and
resulted in ~30% weight reduction. Dr. Pasqualini`s goal is to successfully
translate Prohibitin-TP01 into the clinic as a new agent for obese men with
advanced prostate cancer. 

Kenneth Pienta, MD
University of Michigan

Analysis of Primary and Metastatic Prostate Cancer from Men with Untreated
Prostate Cancer

The goal of this project is to develop a comprehensive biorepository from
individuals with untreated primary and metastatic prostate cancer to 1.) better
define the molecular basis for prostate cancer progression, 2.) discover new
biomarkers of aggressive and potentially lethal prostate cancer, and 3.)
identify new therapeutic targets for this disease. Dr. Pienta and colleagues
have proposed to collect serum, circulating tumor cells (cancer cells that broke
away from the tumor and entered circulation), DNA, plasma, urine and biopsies
from the primary tumor and metastatic sites including bone, lymph nodes and
other soft tissue sites of cancer involvement. This biospecimen repository will
be unique because these patients` metastatic site samples are pre-treatment.
Autopsy specimens of metastatic prostate cancer that had been treated are
useful. However, the selective pressure of long-term treatment exposure causes
distinct molecular changes and cellular selection of a patient`s tumor cells
which complicates molecular studies of tumor progression and hinders the
identification of therapeutic targets. All of these biospecimens will be
analyzed using high-throughput molecular biotechnologies and will be made
available to the global research community. 

Matthew Rettig, MD
University of California, Los Angeles

A Nano-Structured Platform for Enhanced Detection of CTCs in Prostate Cancer
Patients

Circulating tumor cells (CTCs) are cancer cells that break away from either the
primary tumor or metastatic lesions and enter blood in circulation. There is
great interest in CTCs because they have the potential to provide clinicians
with vital information of a patients` cancer and are accessible ("liquid
biopsy") without having to perform an invasive tumor tissue biopsy. CTCs can be
captured using a variety of technologies. A technical challenge has been to
capture a sufficient number of viable CTCs to conduct molecular studies. Dr.
Rettig and his team at UCLA have developed a novel and inexpensive cell capture
system applying complex nanotechnology and cell biology to collect large numbers
of viable CTCs from patients with metastatic prostate cancer. The collection of
viable CTCs will enable Dr. Rettig`s group to define the molecular alterations
in prostate cancer cells that confer progression and lethality. Ex vivo (outside
of the body) preparations of patient CTCs will also be useful in selecting
appropriate therapies for individual patients and for refining their prognosis.
Success of this project will translate into more informed treatment strategies
and may identify new therapeutic targets. 

Matthew Smith, MD, PhD
Massachusetts General Hospital

Prospective Translational Study of Metformin in Castration-Resistant Prostate
Cancer

Recent population-based studies have shown that type 2 diabetic men treated with
Metformin, a medicine that lowers insulin levels in blood, have lower prostate
cancer incidence and improved prostate cancer specific outcomes. These findings
provoked the hypothesis that higher insulin levels promote prostate cancer
growth. Dr. Smith and colleagues propose to investigate the efficacy of
Metformin in a prospective clinical trial for patients with progressive prostate
cancer who have failed hormonal therapy. During this clinical study the
investigators will monitor changes in the metabolic profile (a catalogue of
hormones and chemical byproducts indicative of cellular processes) of patients`
blood and correlate results with clinical response. This study will provide
essential information on the anti-tumor effects of Metformin and may credential
Metformin as a new agent for prostate cancer therapy. 

Scott Williams, MD
Peter MacCallum Cancer Centre, Australia

Exploration of the Relationship between In Vivo Molecular Imaging, Cellular
Response and Therapeutic Outcome in Irradiated Human Prostate Cancer

A common treatment for localized prostate cancer is radiation therapy.
Currently, the two most widely used types of radiation therapy are external beam
radiation and brachytherapy (implantation of radioactive seeds into the prostate
gland). Yet given the frequency of radiation therapy procedures, few studies
have explored how patient tumors respond to radiation and why certain tumor
cells are resistant. Dr. Williams` will perform a clinical investigation that
uses molecular imaging and molecular analysis of biopsies before and after
radiation therapy to identify predictive markers of response and resistance to
radiation therapy. This study will advance the optimization of radiation therapy
for prostate cancer patients. 

About the Prostate Cancer Foundation

The Prostate Cancer Foundation (PCF) is the world`s largest philanthropic source
of support for accelerating the world`s most promising research for discovering
better treatments and cures for prostate cancer. Founded in 1993, the PCF has
raised nearly $400 million and provided funding to more than 1,500 researchers
at nearly 200 institutions worldwide. PCF advocates for greater awareness of
prostate cancer and more efficient investment of governmental research funds for
transformational cancer research. Its efforts have helped produce a 20-fold
increase in government funding for prostate cancer. More information about the
PCF can be found at www.pcf.org.

Prostate Cancer Foundation
Dan Zenka, APR
Vice President, Communications
310-570-4714
dzenka@pcf.org

Copyright Business Wire 2010

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