Following a rigorous peer review process, PCF selected 10 Creativity Award recipients from more than 300 applications representing 105 institutions in 11 countries.
The projects represent a range of research areas, from biomarkers for earlier and more precise detection and treatment to the development of new, nano-enabled therapeutics for metastases.
First-time PCF Award Recipient
Cory Abate-Shen, PhD – Columbia University Medical Center
A Novel Human-to-Mouse-to-Human Approach for the Elucidation of Prostate Cancer Pathways and Druggable Targets—Identifying Shared Human and Mouse Molecules May Eliminate Traditional Limitations of Animal Models and Speed New Drug Intervention
This project will compare all dysfunctional regulatory and signaling molecules in common between mouse prostate cancer and human prostate cancer. These molecules may represent a new set of “druggable” targets. Unlike typical drug discovery processes, where animal models are of questionable relevance to human biology, common genes and pathways between man and mouse prostate cancer should be fully amenable to animal model testing. This creative project promises to generate new targets for therapeutic intervention in prostate cancer and speed their development.
The Charlie Wilson Creativity Award
Adam Dicker, MD, PhD, Karen Knudsen, PhD – Thomas Jefferson University
Self-Seeding and Radiation Therapy: A New Strategy Against Metastatic Prostate Cancer—Preventing Circulating Prostate Cancer Cells from “Re-Seeding” in the Prostate May Change the Behavior of Metastatic Cells
The mechanism by which prostate cancer metastasizes is not fully understood. The decades-old theory is that prostate cancer cells (the seed) leave the prostate, enter circulation, and invade an environment conducive to growth (the soil) such as lymph nodes and bone. Dr. Dicker proposes to test a new theory of metastasis called self seeding where circulating tumor cells leave distant sites and return to their most desired environment, the prostate, where they are “re-energized” and sent back to circulation to further disseminate. This project will test the possibility that radiation therapy to an intraprostatic tumor in mice will interrupt the metastatic behavior of a distant metastasis by destroying the conditioning provided by the prostate. If successful, this concept can be rapidly translated to the clinic as an anti-metastasis therapeutic strategy.
The Michael Vinecki Creativity Award
Shelton Earp, MD – University of North Carolina
Application of Nanotechnology to Novel Models of Prostate Cancer—Nanoscale Fabrication Technology May Provide New Modeling Capabilities and Therapies to Arrest Lethal PCa Progression
This program has discovered that a molecule named Ack1 can cause poorly-tumorigenic prostate cancer cells to become highly lethal. In addition, it has developed an innovative nanoparticle drug delivery technology using the same stepped layering and etch process used in the fabrication of today’s nanoscale semiconductors and microprocessors. The nanotherapy involves delivery of drugs in nanoscale discs that look like hockey pucks and are flexible like red blood cells as they circulate through capillaries. Inhibitors of Ack1 will be delivered to novel models of prostate cancer to credential the Ack1 target for discovery of new therapies for prostate cancer. Ultimately, it is hoped that Ack1 inhibitors delivered by flexile nanodiscs would be able to shut down the lethal progression of prostate cancer cells.
Barbara Graves, PhD – University of Utah
ETS Protein Targets in Prostate Cancer—Understanding Gene Activity that Likely Causes Up to 60 Percent of Prostate Cancer Cases Can Open Door to New Drug Development
Over-expression of Ets genes, due to chromosomal fusions are the likely cause of over 40-60% of prostate cancer cases. Dr. Graves, a world leader in Ets genes in leukemia, proposes to enter the prostate cancer field and to map the DNA regions that bind Ets proteins which will in turn help to define the downstream cancer causing factors. This proposal intends to employ state-of-the-art molecular biology biotechnologies. It also recruits into prostate cancer research one of the original leading scientists studying Ets genes prior to their discovery in prostate cancer at the University of Michigan. These studies could represent the first step in discovering new medicines that could interrupt carcinogenesis of the prostate and progression of prostate cancer that occurs via Ets genes.
David Heber, MD, PhD – University of California, Los Angeles
Development of an Ex Vivo Bioassay to Examine Modulation of PSA-Positive Macrophage Invasiveness and Inflammatory Activities in Prostate Cancer Patients with Abdominal Obesity—The Identification of New Biomarkers May Be Able to Assess the Effectiveness of Diet and Lifestyle Changes
Macrophages are specialized white blood cells that scavenge invading microbes and dead cellular material. They are also involved in inflammation, angiogenesis, and metastasis. Accumulated abdominal fat and metabolic syndrome, two common findings in prostate cancer patients, activates macrophages. However, this activity is reversible with diet and lifestyle changes. This creative project proposes to study prostate cancer-associated macrophages both in the lab and in patients. These cancer-associated macrophages will be tested as a progression biomarker for successful alterations in lifestyle and might represent a meaningful endpoint for pharmacological intervention between obesity and inflammation.
Towia Libermann, PhD, Alan Rigby, PhD – Beth Israel Deaconess Medical Center
Development and Validation of Selective Small Molecule Ets Factor Inhibitors for Prostate Cancer—Understanding Gene Activity that Likely Causes Up to 60 Percent of Prostate Cancer Cases Can Open Door to New Drug Development—Another Approach
The genetic alteration present in 40-60% of prostate cancer cases gives rise to expression of Ets factors that drive the initiation and progression of prostate cancer. Identification of the Ets factor binding sites on DNA is the first step in selecting candidate inhibitors of the highly carcinogenic event. In contrast to Dr. Barbara Graves’ Creativity Award, where advanced molecular biology biotechnologies will be used to identify these sites, Drs. Libermann and Rigby will use state-of-the-art computer-aided drug design methods and biocomputational models to model the structure of these sites. In fact, this work has already identified a series of candidate lead compounds that block Ets binding to DNA. If successful, this work could generate drug candidates to block prostate cancer progression.
The Dan Fogelberg Creativity Award
David Nanus, MD – Weill Cornell Medical College
PSMA-based Microfluidics-Capture of Circulating Prostate Cancer Cells: Study of Microtubule-driven Androgen Receptor Signaling, Gene Fusion, and Gene Expression Profiles with Correlation to Clinical Response to Taxane Therapy—New Capture Technology for Circulating Tumor Cells Supported by PCF-Funding May Prove Useful in Identifying Patients Most Likely to Benefit from Taxotere.
This project combines, for the first time, an advanced system to capture circulating prostate cancer cells from whole blood with the discovery of a set of biomarkers that may predict sensitivity to Taxotere. While clinical investigations have already shown that Taxotere prolongs survival for advanced prostate cancer patients, this new biotechnology with “liquid biopsies containing circulating prostate cancer cells” could predict which individuals are most likely to respond to this therapy while sparing many from unnecessary side effects.
Pier Paolo Pandolfi, MD, PhD – Beth Israel Deaconess Medical Center
Pro-Senescence Therapy for Cancer: A Novel Approach Towards Prostate Cancer Prevention and Cure—Identifying New Druggable Targets May Enable Scientists to Lull Prostate Cancer Cells to Sleep
Cellular senescence is a process whereby a cancer cell essentially “goes to sleep”. Dr. Pandolfi has discovered several druggable cellular signaling “nodes” that act together to cause a heretofore unknown form of senescence in prostate cancer cells. He believes that this process is also operative in the very difficult to eradicate cancer stem cell population. Chemical compounds against these targets that will drive prostate cancer cells into a state of senescence will be evaluated in specialized animal models of prostate cancer with the goal of clinical translation.
The Arnie’s Army Creativity Award
Muneesh Tewari, MD, PhD – Fred Hutchinson Cancer Research Center and University of Washington
Exosomal RNAs as Serum Prostate Cancer Biomarkers—Personalized Treatment and Better Prognostic Indicators May Become Reality Through MicroRNA Tumor Profiling
MicroRNAs, small RNA molecules that regulate gene expression, have been found to circulate in blood within lipid membrane-encased particles (exosomes) that are secreted from and blebbed off of cancer cells. These molecules which are “spit” into the blood stream appear cancer-specific and hold great promise for molecular profiling of tumors. This project is on the cutting edge of a new technology whereby diagnosis, prognosis and optimal treatment strategy might be determined by analysis of circulating microRNAs. Dr. Tewari will optimize the isolation of exosomes and purification of microRNAs from prostate cancer models followed by genetic probing of these materials. This technology may ultimately be useful to patients for personalized treatment and improved prognostic information and is utterly original.
The William Bikoff Creativity Award
John F. Ward, MD – The University of Texas MD Anderson Cancer Center
Noninvasive Radiofrequency Field for the Targeted Destruction of Prostate Cancer Using Directed Gold Nanoparticles—Activated Gold Particles Could Provide Novel Means of Destroying Tumors
This project combines cutting-edge nanotechnology with high-tech radio frequency energy to heat prostate cancer cells to death. Gold nanoparticles will be targeted to prostate cancer and injected intravenously to seek all sites of metastasis. Harmless penetrating radio frequency will heat the particles localized in tumor sites thereby killing the malignancy with little destruction of non-targeted cells. Studies will first employ model systems with a goal of entering the clinic in about three years.
Terms to know from this article:
A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called a lymph gland.
The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a "metastatic tumor" or a "metastasis." The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-ta-seez).
Increase in the size of a tumor or spread of cancer in the body.
A measurable biological substance that can be used to indicate disease characteristics such as diagnosis, prognosis, or therapeutic responses.
A type of hormone that promotes the development and maintenance of male sex characteristics.
The likely outcome or course of a disease; the chance of recovery or recurrence.
A mass of excess tissue that results from abnormal cell division. Tumors perform no useful body function. They may be benign (not cancerous) or malignant (cancerous).
Abbreviation for prostate cancer; CaP is also used.
The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
prostate-specific antigen (PSA): A substance produced by the prostate that may be found in an increased amount in the blood of men who have prostate cancer, benign prostatic hyperplasia, or infection or inflammation of the prostate.