PCF funds 14 new Creativity Awards for advanced prostate cancer research

Jun 2 2011

The Prostate Cancer Foundation (PCF) today announced that it has funded 14 new Creativity Awards for advanced prostate cancer research. These two-year awards are designed to support innovative research ideas that have the potential to achieve breakthroughs for improved prostate cancer diagnosis and treatment. PCF Creativity Awards aid the advancement of the world's most imaginative, new research ideas that are not yet funded by any government or foundation sources.

The funded projects represent a range of research areas including biomarkers for earlier and more precise detection and treatment, the development of new, nano-enabled therapeutics for patients with metastatic disease, and identifying new targets for drug development.

"We were impressed with the unique ideas represented by the applicants. A rigorous process that included 71 peer reviewers vetted the 14 selected treatment sciences projects from a field of more than 200 applications representing leading institutions in 10 countries," reports Howard Soule, PhD, executive vice president and chief science officer for PCF. "These awards fortify our pipeline of compelling ideas to cultivate new solutions for the prostate cancer problem. We believe that our investment in these projects will push scientific discovery and deliver better therapies for patients with advanced prostate cancer."

Historically, 70 percent of such PCF awards have gone on to attract additional multi-year funding from PCF and other sources within three years of their original funding by PCF.

"Eight of the awards are going to investigators who have never before been funded by PCF and we are very excited to track the progress of these new ideas." added Dr. Soule. "They have enormous potential to deliver breakthrough discoveries and ultimately enable physicians to cure more and overtreat less."

2011 Creativity Award Recipients

Steve Cho, MD
Assistant Professor of Radiology
The Johns Hopkins University School of Medicine

Proposal Title: Evaluation of PSMA-based PET as Functional Imaging Biomarker of Primary Prostate Cancer

A major unmet medical need in prostate cancer diagnosis and therapy is the ability to image small metastatic tumors. This proposal will develop a functional imaging biomarker specific to prostate cancer. This PET (positron emission tomography-a nuclear imaging technique) imaging tracer, already shown specific for prostate cancer by imaging studies in patients, will be tested for detection of bone and nodal metastases at time of original prostate cancer diagnosis. This imaging system has the potential to more specifically stage prostate cancer patients prior to initial therapy and determine those who might benefit from early aggressive therapy. Dr. Cho transitioned a 2007 PCF Young Investigator Award into this PCF grant.

Potential patient benefit: The ability to detect early metastatic prostate cancer and to identify patients who will benefit from early aggressive treatment may prolong survival in an important subset of individuals.

Samuel Denmeade, MD
Professor, Pharmacology & Molecular Sciences
The Johns Hopkins University School of Medicine

Proposal Title: Evaluation of Bindarit, a Novel Inhibitor of the CCL2 Chemokine Axis, as Therapy for Metastatic Prostate Cancer

Dr. Denmeade is testing a medication called Bindarit - an orally active compound already tested in over 500 patients. Bindarit affects a number of mediators of chemotherapy resistance, especially in bone. Preclinical studies will be performed to qualify Bindarit for testing in men with metastatic prostate cancer.

Patient benefit: Bindarit may represent a new and novel tumor microenvironment therapy for men with metastatic prostate cancer and holds the potential to improve the efficacy of chemotherapy.

* Peter B. Dervan, PhD
Bren Professor of Chemistry
California Institute of Technology

The Susan and James Blair-PCF Creativity Award

Proposal Title: DNA-binding Polyamides as Inhibitors of TMPRSS2-ERG Activity in Prostate Cancer

The recent discovery of gene fusions in prostate cancer has established a new biological mechanism for expression of cancer causing genes (oncogenes). Dr. Dervan has developed a chemistry for producing oncogene inhibitors that is more creative and has higher potential than any pharmaceutical program in stopping oncogene activity. Oncogene inhibitors that block their interaction with specific genomic regions will represent a new class of medication for metastatic prostate cancer.

Potential patient benefit: This work has the potential to discover new targeted therapies for metastatic prostate cancer with an entirely new type of chemistry.

* Christian R. Gomez, PhD
Research Associate
The Mayo Clinic
Facultad de Medicina, Universidad Diego Portales, Santiago, Chile

Proposal Title: Hypoxia-Regulated DLG7 in Prostate Carcinogenesis and Prognosis

An unmet medical need in prostate cancer diagnosis and therapy is the lack of highly-reliable progression biomarkers to monitor efficacy of therapy. Dr. Gomez's research team has discovered a molecule called DLG7 which may serve as a reliable progression biomarker in prostate cancer. This research will test the ability of DLG7 and related molecules to predict an unfavorable outcome of prostate cancer by testing patient biopsy specimens that are well annotated with outcome data.

Potential patient benefit: While PSA is a useful biomarker, it is prostate-specific and not prostate cancer-specific early in the prognostic process. DLG7 has the potential to be a prostate cancer-specific marker that may accurately predict the process of disease progression.

Beatrice Knudsen, MD, PhD
Medical Director of Biorepository and Translational Pathology
Cedars-Sinai Medical Center

Proposal Title: Biomarkers of Response to Treatment with XL184 in the Bone

XL184 (caboxantanib) is a new experimental medication for metastatic prostate cancer with promising clinical results. To more effectively administer XL184 to patients with metastatic prostate cancer, Dr. Knudsen seeks to define the precise anti-cancer mechanism of action. She has assembled a team at Cedars-Sinai in Los Angeles and University of Washington/Fred Hutchinson Cancer Institute in Seattle to study the effects of XL184 in patient biopsies and will investigate the mechanism of action of this encouraging agent as a biomarker for response in patients.

Potential patient benefit: An understanding of the mechanism of action of XL184 will accelerate the clinical development of this very encouraging agent by providing investigators with laboratory and imaging biomarkers of response.

* Kit Lam, MD, PhD
Professor of Medicine
Chief, Division of Hematology/Oncology, Department of Internal Medicine
UC Davis Medical Center

Proposal Title: Smart Nanoparticles for Imaging and Treatment of Prostate Cancer

Dr. Lam is an expert in the area of nanotechnology drug delivery systems. His research group has invented a nanoparticle that delivers chemotherapy only to prostate cancer cells. These targeted nanoparticles will be loaded with chemotherapy medications and will be tested for targeting in animal models of prostate cancer. It is hoped that these particles will deliver concentrations of chemotherapy directly to tumors that far exceed therapeutic levels that can be achieved by standard intravenous administration.

Potential patient benefit: This delivery system could improve the efficacy of Docetaxel many-fold, thereby improving survival efficacy while reducing side effects.

* Glenn Liu, MD
Assistant Professor of Medicine
University of Wisconsin School of Medicine and Public Health
UW Carbone Cancer Center

Proposal Title: Developing a Novel Quantitative Total Bone Imaging (QTBI) Methodology to Assess Treatment Response in Metastatic Prostate Cancer

The lack of ability to measure tumor response in bone has greatly hindered prostate cancer drug development. This project will evaluate the role of functional, qualitative, total bone imaging to assess therapeutic response to new medicines in bone metastases. A PET/CT scan index will be established to estimate percent bone involvement and to determine total burden of disease in bone.

Potential patient benefit: Development and measurement of this imaging biomarker will accelerate our ability to count cancer cells in patients and will speed the drug development process by more accurately and rapidly assessing tumor response in bone. The method may provide physicians with a better way to assess the progression and regression of prostate cancer.

Peter Nelson, MD
Full Member
Fred Hutchinson Cancer Research Center
Professor of Oncology, Adjunct Professor Genome Science and Pathology
University of Washington

Proposal Title: Targeting Therapy-Induced Resistance Mechanisms in the Prostate Tumor Microenvironment

Dr. Nelson postulates that chemotherapy resistance originates in the tumor microenvironment in response to stress caused by chemotherapy. He has discovered that tumor cell repopulation accelerates during the intervals between courses of treatment causing resistance to further chemotherapy. This proposal seeks to understand the series of events occurring in the tumor microenvironment resulting in resistance to chemotherapy.

Potential patient benefit: An understanding of the series of biologically programmed events in the tumor microenvironment that cause chemotherapy resistance will lead to resensitization strategies and improved efficacy of chemotherapy, the mainstay treatment for metastatic prostate cancer.

* William Polkinghorn, MD
Research Fellow
Memorial Sloan-Kettering Cancer Center

Proposal Title: Defining the role of AR Signaling in Promoting Prostate Cancer Radioresistance

Dr. Polkinghorn postulates that androgen receptor signaling directly promotes prostate cancer resistance to radiation therapy (radioresistance). This work will determine which androgen receptor-dependent genes promote prostate cancer radioresistance. Medical inhibition of androgen pathway gene expression targets could increase efficacy of radiation therapy. Testing will be performed in prostate cancer cell lines as well as human prostate cancer tissue specimens from large clinical trials of androgen deprivation therapy during radiation treatment with known outcomes.

Potential patient benefit: More effective radiation therapy of localized and locally advanced prostate cancer may result in the prevention of metastatic disease years, if not decades, later.

* Ulrich Rodeck, MD, PhD
Professor, Department of Dermatology & Cutaneous Biology
Jefferson Medical College-Thomas Jefferson University

The Ben Franklin-PCF Creativity Award

Proposal Title: Improving the Therapeutic Window of Radiation Therapy for Prostate Cancer

Radiation therapy of locally advanced prostate cancer is associated with severe toxicity limits. Dr. Rodeck will test the hypothesis that modulators of inflammation will preferentially protect normal tissues, but not tumor tissues against radiation-associated toxicity. A series of novel radioprotective compounds have been selected to test this hypothesis in models of prostate cancer and in patients.

Potential patient benefit: This radiobiology proposal will allow higher doses of external beam radiation to be administered, resulting in improved cancer control with reduced side effects to normal adjacent tissue.

* Marianne Sadar, PhD
Senior Scientist, Michael Smith Genome Sciences Centre, BC Cancer Agency
Honorary Associate Professor, Department of Pathology and Laboratory Medicine
University of British Columbia

Proposal Title: Niphatenones a Completely New Class of Androgen Receptor Antagonist

Dr. Sadar has discovered and is developing compounds derived from undersea plant life for development of new treatments for metastatic prostate cancer. Some of these compounds block the activation of the androgen receptor and possess antitumor activity. These compounds, called niphatenones, will be thoroughly investigated as clinical therapeutic candidates for treatment of metastatic prostate cancer.

Potential patient benefit: Niphatenones represent a new class of antineoplastic medication for treatment of metastatic prostate cancer.

Matthew R. Smith, MD, PhD
Associate Professor, Department of Medicine, Harvard Medical School
Assistant in Medicine, Hematology/Oncology
Massachusetts General Hospital Cancer Center

Proposal Title: Prospective Translational Study of XL184, a Dual Inhibitor of VEGFR2 and MET, in Men with Castration-Resistant Prostate Cancer (CRPC) and Bone Metastases

XL184 (caboxantanib), a new and highly encouraging medicine for the treatment of metastatic prostate cancer is in very early stages of clinical development. One significant goal of this proposal is to establish efficacy and safety of XL184 at lower doses to reduce toxicity and increase time on treatment. The rapid bone scan improvement in patients treated with XL184 will be examined with MR imaging technology to better define the significance of this unprecedented finding.

Potential patient benefit: Determining the lowest effective dose of XL184 will establish a safer protocol for administering this very encouraging new treatment for metastatic prostate cancer.

Owen Witte, MD
Distinguished Professor of Microbiology, Immunology, and Molecular Genetics
President's Chair in Developmental Immunology
David Geffen School of Medicine
University of California, Los Angeles

Proposal Title: Target identification Combining In Vivo Tissue Transformation with Multi-parameter Profiling and "Surprisal Analysis"

The goal of this highly creative proposal is to search for and discover new pathways and therapeutic targets in advanced prostate cancer for therapeutic destruction of disease. A "first-in-field" mathematical modeling and statistical tool has been invented and will be used to discover gene expression patterns and protein modification events that correlate with disease progression yielding new pathways and targets. Findings from this mathematical analysis will be tested in human prostate tumors, as well as in mouse models of prostate cancer.

Potential patient benefit: Great progress has been made in development of new therapies for metastatic prostate cancer; however, the targets elucidated through this Creativity Award could provide an entirely new generation of medicines for metastatic prostate cancer.

Bruce Zetter, PhD
Professor of Cancer Biology, Department of Surgery
Harvard Medical School
Dana-Farber/Harvard Cancer Center

Proposal Title: The Mesenchymal-to-Epithelial Transition (MET) as a Novel Target for Treatment of Disseminated (Metastatic) Prostate Cancer

Epithelial-mesenchymal transition (EMT) is a programmed loss of cell adhesion accompanied by increased cell motility that is thought to be essential for tumor metastasis. However, this process is reversed (mesenchymal to epithelial transition--MET) over time in prostate cancer when disease is widely metastatic, making it adhesive once again. An animal model of prostate cancer MET will be used to obtain a genetic signature of this process. Methods will be established to block MET, which likely represents a lethal form of progressive prostate cancer.

Potential patient benefit: This work will lead to an understanding of mechanisms of metastasis for which new drugs can be designed to inhibit this lethal process.

Source: Prostate Cancer Foundation