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PCF funds 14 new Creativity Awards for advanced prostate cancer research

April 02, 2017

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, PhDProfessor, Department of Dermatology & Cutaneous BiologyJefferson 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, PhDSenior Scientist, Michael Smith Genome Sciences Centre, BC Cancer AgencyHonorary Associate Professor, Department of Pathology and Laboratory MedicineUniversity 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, PhDAssociate Professor, Department of Medicine, Harvard Medical SchoolAssistant in Medicine, Hematology/OncologyMassachusetts 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, MDDistinguished Professor of Microbiology, Immunology, and Molecular GeneticsPresident's Chair in Developmental ImmunologyDavid Geffen School of MedicineUniversity 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, PhDProfessor of Cancer Biology, Department of SurgeryHarvard Medical SchoolDana-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