The PCF Young Investigator Award-Class of 2013 recipients are:
2013 Steve Wynn-PCF Young Investigator
Emmanuel Antonarakis, MD
Johns Hopkins University School of Medicine
Mentors: Michael Carducci, MD and Jun Luo, PhD
Project Title: Understanding mechanisms of response and resistance to abiraterone (Zytiga) and enzalutamide (Xtandi) in men with metastatic castration-resistant prostate cancer, by interrogation of tumor biopsies for androgen receptor splice variants
Description:
- Understanding resistance to new treatments for advanced, metastatic prostate cancer represents an unmet medical need.
- Dr. Antonarakis is studying genetic variants of the target of these new medicines as one possible mechanism for resistance.
- Understanding the genetic basis for resistance to Zytiga and Xtandi can lead to improved use of these treatments and should reveal new targets for treating these highly drug-resistant patients.
What this means to patients: Understanding mechanisms of resistance to Xtandi and Zytiga should lead to improved therapy for treatment-resistant patients with advanced, metastatic prostate cancer.
2013 Millennium Pharma-PCF Y
oung Investigator
Vivek Arora, MD, PhD
Memorial Sloan-Kettering Cancer Center
Mentor: Charles Sawyers, MD
Project Title: Defining strategies to overcome enzalutamide (Xtandi) resistance
Description:
- Preclinical assessment of mechanisms of resistance to hormone therapy in prostate cancer has led to the discovery and development of a new medicine, named ARN-509.
- Dr. Arora has shown that one mechanism of resistance to ARN-509 is the induction of a new hormone receptor, designated Glucocorticoid Receptor (GR).
- It is believed that GR can, in part, replace the androgen receptor, the engine of prostate cancer progression, causing the patient to become drug resistant.
- Dr. Arora will test this idea in models of progressive disease and prostate cancer patients, with inhibitors of GR.
What this means to patients: A qualified inhibitor to the glucocorticoid receptor (GR) could be a new treatment for drug-resistant patients with advanced, metastatic prostate cancer.
2013 The Republic of Tea-PCF Young Investigator
Irfan Asangani, PhD
University of Michigan
Mentor: Arul Chinnaiyan, MD, PhD
Project Title: Characterization and therapeutic targeting of MMSET in prostate cancer
Description:
- The organization of DNA into super-structures is an ordered and normal process of cell growth that is dysregulated in cancer.
- Chemical modifications of DNA have been identified by Dr. Irfan Asangani as a potential driver of cancer progression.
- One protein, MMSET, in this dysregulated program of DNA modification has been identified as an anti-cancer target by Dr. Asangani’s mentor, PCF-funded researcher, Dr. Arul Chinnaiyan.
- Inhibitors of MMSET have been discovered in this lab and will be characterized for their anti-cancer properties in the course of this research.
What this means to patients: Dr. Asangani has identified a new target with a novel mechanism of action for prostate cancer therapy. A new experimental medicine targeting this protein will be developed for the treatment of advanced, metastatic prostate cancer.
2013 Millennium Pharma-PCF Young Investigator
Jennifer Bishop, PhD
University of British Columbia
Mentors: Martin Gleave, MD and Amina Zoubeidi, PhD
Project Title: Regulation of cell plasticity by the androgen receptor: A novel mechanism of enzalutamide (Xtandi) resistance
Description:
- Approximately 25% of patients who fail Xtandi and Zytiga present with a lethal form of prostate cancer named neuroendocrine prostate cancer (NEPC).
- Features of NEPC include changes in hormonal sensitivity, and characteristics of cells that initiate cancer (cancer stem cells).
- Dr. Bishop will investigate NEPC for new therapeutic targets in treatment-resistant disease.
What this means for patients: Dr. Bishop is investigating cellular mechanisms that lead to the development of resistance to Zytiga and Xtandi. This insight into the breadth of the tumor cell response mechanisms should help improve the efficacy of Xtandi and lead to the discovery of other therapeutic targets for treatment-resistant prostate cancer patients.
2013 Michael & Lori Milken-PCF Young Investigator
Qi Cao, PhD
University of Michigan School of Medicine
Mentor: Arul Chinnaiyan, MD, PhD
Project Title: A novel role for Polycomb Group proteins in androgen signaling and prostate cancer
Description:
- A family of proteins known as the Polycomb Group (PcG) regulates gene expression in cellular development in normal cells, and is partially responsible for gene expression dysregulation in cancer.
- PcG proteins are upregulated in prostate cancer and promote disease progression and metastasis. Therefore, these proteins are therapeutic targets.
- One specific PcG protein is named EZH2. Inhibitors of EZH2 will be investigated for the treatment of advanced metastatic prostate cancer.
What this means for patients: Dr. Cao is working on unraveling the underlying mechanisms that lead to cancer progression and the development of treatment resistance. He will also evaluate a combination of two targeted inhibitors of EZH2 for the treatment of advanced prostate cancer.
2013 Steve Wynn-PCF Young Investigator
Charles Chan, PhD
Stanford University School of Medicine
Mentors: Irving Weissman, MD and Michael Longaker, MD
Project Title: Identification and therapeutic targeting of cancer stem cell niche interactions in metastatic prostate bone marrow disease
Description:
- Engraftment of prostate cancer in bone heralds a lethal form of the disease.
- New targets are needed for the treatment of prostate cancer in bone and to prevent bone localization altogether.
- Dr. Chan has discovered a type of metastatic prostate cancer stem cell that can home to bone and grow, causing increased morbidity.
- These investigations are aimed at inhibiting bone-derived factors that permit the localization and proliferation of prostate cancer in the bony environment.
What this means for patients: Dr. Chan proposes to study mechanisms of prostate cancer tumor engraftment in the bone. These studies will identify therapeutic targets to reduce this serious metastatic event.
2013 Steve Wynn-PCF Young Investigator
Chia-Yi Chu, PhD
Cedars-Sinai Medical Center
Mentor: Leland Chung, PhD
Project Title: Metastasis-initiating cells (MICs) as predictors of lethal progression of human prostate cancer
Description:
- An unmet medical need is the control of metastases of prostate cancer that cause the lethal form of this disease.
- Dr. Chu has discovered metastasis-initiating prostate cancer cells that circulate in the blood of animals bearing prostate tumors.
- Novel methods to isolate and characterize circulating tumor cells will be employed in patients to determine if metastasis-initiating prostate cancer cells circulate in man.
What this means for patients: Understanding the biology of metastasis-initiating cells could inform new targets for slowing/inhibiting the lethal metastatic process. In addition, measurement of metastasis-initiating cells in the setting of active surveillance for primary prostate cancer could better stratify patients who may benefit from early and aggressive clinical intervention.
2013 Astellas Scientific and Medical Affairs, Inc. and Medivation, Inc. – PCF Young Investigator Award
Jason Efstathiou, MD, DPhil
Harvard: Massachusetts General Hospital (MGH)
Mentor: Matthew Smith, MD, PhD
Project Title: Predictors of Response and Failure to Radiotherapy for Prostate Cancer in a Randomized Trial
Description:
- There is a critical unmet need for predictive and prognostic biomarkers that can improve the appropriate tailoring of therapy for localized prostate cancer.
- Dr. Efstathiou is conducting a randomized clinical trial testing the efficacy, side effects, and costs of intensity modulated radiotherapy (IMRT) vs. proton beam therapy for the treatment of men with localized prostate cancer.
- Samples from these patients will also be studied to identify biomarkers of prostate cancer behavior and response to radiotherapy.
What this means for patients: This study will establish the relative clinical benefits, costs, and side effects of IMRT vs. proton beam therapy, and identify biomarkers to tailor the selection of men who are likely to benefit from these treatments.
2013 David H. Koch-PCF Young Investigator
Michael Evans, PhD
Memorial Sloan-Kettering Cancer Center
Mentors: Charles Sawyers, MD and Jason Lewis, PhD
Project Title: Exploiting the genetics of advanced prostate cancer for tumor detection and therapy with transferrin-based radionuclides
Description:
- Molecular imaging of prostate cancer to determine sites of metastasis in recurrent patients is an unmet medical need.
- Dr. Evans is exploiting the activation of two cancer-causing genes (MYC and PI3K) in prostate cancer, which results in high expression of the transferrin receptor (TfR).
- TfR will be exploited in these studies to image and treat advanced, metastatic prostate cancer with radioactive transferrin.
- The biology underlying this research has great potential to improve imaging and therapy of prostate cancer.
What this means to patients: Two common aberrantly activated genes that drive prostate cancer progression are MYC and PI3K. Dr. Evans is evaluating strategies that employ radioactive transferrin agents as potential diagnostics and therapeutics for the subset of prostate cancers that are driven by MYC and PI3K.
2013 Stanley Zax-PCF Young Investigator
Geraldine Gueron, PhD
Iquibicen-Conicet (Argentina)
Mentor: Elba Vazquez, PhD
Project Title: Proteome-base biomarkers in prostate cancer: protein profiling using mass spectrometry, bioinformatics based approach and tissue microarray technology
Description:
- Proteomics is the study of proteins in a cell and their interactions with each other.
- The overall goal of this research is to use proteomics for the identification of predictive prostate cancer disease biomarkers.
- Dr. Gueron has demonstrated that a protein designated Heme Oxygenase-1 (HO-1) is involved in prostate cancer etiology and that it directly interacts with other cancer-causing proteins involved in cell signaling.
- Studying the interaction of HO-1 and other cell signaling molecules is significant because it is believed to regulate the engine of prostate cancer – the androgen receptor.
What this means for patients: This novel targeted proteomics study may do two things: 1) develop a laboratory test that will predict the presence of potentially lethal prostate cancer and 2) discover targets for the treatment of advanced metastatic prostate cancer.
2013 PCF Young Investigator
Lauren Harshman, MD
Dana-Farber Cancer Institute
Mentors: Philip Kantoff, MD and Christopher Sweeney, MBBS
Project Title: Clinical exploration of innovative targeted and immune modulating therapies in prostate cancer
Description:
- Immunotherapy has come of age with the approval of Sipuleucel-T (Provenge) and the introduction of ipilimumab (Yervoy) and other similar immune modulators into clinical trials for advanced metastatic prostate cancer.
- Dr. Harshman will study the biologic activities of a genetically-modified prostate tumor cell vaccine in the setting of Xtandi (enzalutamide) therapy for advanced, metastatic prostate cancer.
- These translational investigations, while developing a new therapy for patients, will also result in a biological understanding of the mechanisms of sensitivity and resistance to immunotherapy for prostate cancer. What this means for patients: A new immunotherapy will be developed for advanced, metastatic prostate cancer.
What this means for patients: A new immunotherapy will be developed for advanced, metastatic prostate cancer.
2013 PCF China Young Investigator in Honor of Stanley Zax
Hao Hu, MD, MBBS
People’s Hospital, Peking University
Mentors: Kexin Xu, MD, MBBS and Xiaofeng Wang, MBBS
Project Title: EMI1 and its role in prostate cancer initiation and progression.
Description:
- Dr. Hu’s research program will focus on the mechanisms of prostate cancer initiation and progression. He and his team have identified the protein EMI1 (Early Mitotic Inhibitor 1) as playing a crucial role in disease development and progression by interacting with the androgen receptor, the primary driver of prostate cancer.
- His team will study the role of EMI1 on the progression of prostate cancer to disease that is resistant to treatment.
- Inactivation of EMI1 may be a therapeutic strategy against the development and progression of treatment- resistant prostate cancer.
What this means to patients: EMI1 represents a potential target for new drug development. If successful, patients would have a new therapy to prevent resistance to treatment of advanced disease.
2013 David and Judy Fleischer-PCF Young Investigator
Theodoros Karantanos, MD
MD Anderson Cancer Center
Mentors: Timothy Thompson, PhD and Christopher Logothetis, MD
Project Title: The role of aerobic glycolysis in the development of castrate resistant prostate cancer
Description:
- Certain oncogenic molecules in prostate cancer cells regulate cellular metabolism in the tumor microenvironment, allowing tumor cells to proliferate under harsh conditions.
- Dr. Karantanos believes that a program of oncogenic signaling proteins is involved in lethal forms of prostate cancer.
- Studies will be performed to assess whether targeting metabolic pathways and cell signaling pathways together can reduce the lethality of prostate cancer.
What this means for patients: Dr. Karantanos is working on identifying the underlying biologic factors that lead to the massive up-regulation of energy production pathways in tumor cells that support their rapid proliferation. This work holds the potential to identify both biomarkers and drug targets to specifically inhibit the oncogenic signaling that promotes cancer progression.
2013 Steve Wynn-PCF Young Investigator
Aaron LeBeau, PhD
University of California, San Francisco
Mentors: Henry VanBrocklin, PhD and Phillip Febbo, MD
Project Title: Targeting active urokinase plasminogen activator for therapy using an internalizing human antibody
Description:
- Prostate tumor cells upregulate and secrete an enzyme named Urokinase Plasminogen Activator (uPA) that specifically degrades other proteins.
- Dr. LeBeau proposes a novel therapy for prostate cancer based on a monoclonal antibody to uPA conjugated to a high-energy radioactive molecule.
- The cellular and biological properties of this new therapy on prostate tumors and surrounding tissues will be investigated.
What this means for patients: Dr. LeBeau is developing potent targeted antibodies that specifically kill prostate cancer cells and their accompanying tumor microenvironment. This work could lead to a new treatment for advanced, metastatic prostate cancer.
2013 Stanley Zax-PCF Young Investigator
Rohit Mehra, MD
University of Michigan School of Medicine
Mentor: Arul Chinnaiyan, MD, PhD
Project Title: Clinicopathological characterization of novel lncRNAs in prostate cancer risk stratification
Description:
- LncRNAs (long non-coding RNAs) are a form of genetic message that do not encode proteins but are highly involved in the expression of other genes.
- PCF-funded researcher, Dr. Arul Chinnaiyan and his team recently described a set of 121 novel lncRNAs implicated in prostate cancer progression. SChLAP1 (Second Chromosome Locus Associated with Prostate-1) was identified as a prostate cancer-specific lncRNA that promotes cell invasion and metastasis in approximately 20% of cases.
- Dr. Mehra proposes to elucidate the associations of SChLAP1 and aggressive prostate cancer.
What this means for patients: These studies will evaluate the association of SChLAP-1 expression with aggressive prostate cancer and should help to stratify patients for risk.
2013 Stanley Zax-PCF Young Investigator
Antonina Mitrofanova, PhD
Columbia University
Mentor: Michael Shen, PhD
Project Title: A systems biology approach to identify and evaluate novel drug targets for aggressive prostate cancer
Description:
- Systems biology is a computational-based inter-disciplinary field of study that focuses on complex interactions within biological systems.
- Dr. Mitrofanova intends to employ systems biology to investigate gene expression regulators of aggressive prostate cancer.
- These investigations should lead to the discovery of treatment targets for the root causes of aggressive disease.
What this means for patients: This systems biology approach to understanding the complexity of aggressive prostate cancer may result in the identification and validation of new treatments.
2013 Joseph Neubauer-PCF Young Investigator
Niv Papo, PhD
Ben-Gurion University of the Negev (Israel)
Mentor: Eyal Mishani, PhD
Project Title: Developing novel dual-specific proteins that target multiple receptors for applications in prostate cancer imaging and therapy
Description:
- Angiogenesis is the process of new blood vessel development, a hallmark of cancer and Prostate Specific Membrane Antigen (PSMA) is a protein expressed on the surface of prostate tumor cells.
- Dr. Papo intends to produce engineered proteins that will simultaneously bind to PSMA on prostate cancer cells and inhibit angiogenesis.
- This engineered protein inhibitor should be a drug candidate for the treatment advanced, metastatic prostate cancer.
What this means for patients: This is a novel therapeutic candidate for the treatment of advanced, metastatic prostate cancer.
2013 Michael & Lori Milken-PCF Young Investigator
Jennifer Rider, ScD
Harvard School of Public Health
Mentors: Lorelei Mucci, ScD and Myles Brown, MD
Project Title: The immunomodulatory and androgen-associated actions of vitamin D in prostate cancer
Description:
- Low vitamin D levels in blood have been shown in numerous population-based studies to correlate with prostate cancer mortality. Also, several genetic alterations in the vitamin-D pathway-related genes have been shown to be associated with a risk of death from prostate cancer.
- Dr. Rider’s studies will investigate a link between vitamin D levels, lethal prostate cancer and the presence of prostatic infection.
- These investigations should contribute to an understanding of the etiology of the lethal form of prostate cancer.
What this means for patients: The outcomes of this research will help stratify patient risk for lethal prostate cancer.
2013 Ben Franklin-PCF Young Investigator
Matthew Schiewer, PhD
Thomas Jefferson University
Mentors: Karen Knudsen, PhD
Project Title: Determining the translation capacity of the PARP-1/AR axis in prostate cancer
Description:
- Deficiencies in the repair of DNA are a hallmark of cancer. A molecule, named PARP, is involved in DNA damage repair. The inhibition of PARP with specific medications is a potential therapy for advanced, metastatic prostate cancer.
- Inhibition of PARP may also reduce cancer progression by reducing the activity of the androgen receptor which is the engine of prostate cancer.
- In these investigations, Dr. Schiewer will study the role of PARP in the modulation of AR activity.
What this means to patients: Understanding the relationship between PARP inhibition and AR activity may provide new therapeutic opportunities for prostate cancer patients with advanced, metastatic disease.
2013 Ben Franklin-PCF Young Investigator
Nicole Simone, MD
Thomas Jefferson University
Mentors: Adam Dicker, MD, PhD, Karen Knudsen, PhD and Peter Carroll, MD
Project Title: Metabolic approaches for targeting multiple components of the IGF-1R pathway in prostate cancer
Description:
- IGF (Insulin-like Growth Factor) receptor is dysregulated during prostate cancer progression.
- Dr. Simone and colleagues have demonstrated that caloric restriction decreases tumor growth and metastases in animal models of prostate cancer, and the activity of the IGF pathway is decreased further by radiation and chemotherapy.
- Clinical trials involving diet modification in prostate cancer patients undergoing radiation or chemotherapy could benefit from these findings.
What this means for patients: Caloric restriction may enhance the efficacy of chemotherapy or radiation for the treatment of prostate cancer.
2013 Steve Wynn-PCF Young Investigator
Daniel Thorek, PhD
Memorial Sloan-Kettering Cancer Center
Mentors: David Scheinberg, MD, PhD and Steve Larson, MD
Project Title: Alpha-particle therapy by 225Actinium-labeled prostate kallikrein-specific antibody to eradicate advanced disease
Description:
- Treatment of advanced, metastatic prostate cancer, although greatly improved with new treatments, still represents an unmet medical need.
- Prostate cancer expresses a molecule called hK2 (human Kallikrein 2), an enzyme similar to PSA.
- Dr. Thorek proposes to direct lethal, alpha-emitting isotope to prostate cancer tumors with a protein that targets hK2. This radioisotope will be internalized by the tumor cell and will result in its total destruction.
What this means for patients: The specific delivery of a radioisotope to prostate tumors represents a new therapy for advanced, metastatic prostate cancer.
2013 Mark R. Shenkman-PCF Young Investigator in Honor of Albert Fuss
Eliezer Van Allen, MD
Dana-Farber Cancer Center
Mentor: Levi Garraway, MD, PhD
Project Title: Dissecting clinical response and resistance to abiraterone acetate (Zytiga)
Description:
- The introduction of Zytiga and Xtandi into standard of care for advanced, metastatic prostate cancer benefits many patients; however, all will ultimately become resistant to these medicines.
- Resistance mechanisms to these treatments remain mainly unknown.
- Dr. Van Allen will interrogate numerous potential resistance mechanisms by determining genomic alterations that occur prior to, and after resistance to Zytiga.
What this means for patients: Understanding mechanisms of resistance to Zytiga should result in the identification of new therapeutic targets for the treatment of drug-resistant, advanced, metastatic prostate cancer.
2013 Ron Perelman-PCF Young Investigator
Li Wang, PhD
Icahn School of Medicine at Mount Sinai
Mentors: William Oh, MD and Eric Schadt, PhD
Project Title: Integrative genomics study of immune signatures in blood and tumor tissue for prostate cancer
Description:
- Identification of biomarkers to stratify risk for prostate cancer patients remains an unmet medical need.
- Dr. Wang proposes to study the genes expressed from all prostate cancer patients seen at Mount Sinai Hospital. Networks of genes involved in the immune response will be selected and assessed through rigorous bioinformatics methods for their prognostic value.
- Ultimately, a predictive model will result for stratifying risk for lethal prostate cancer.
What this means for patients: The results of this study should provide an accurate prediction of survival for patients with advanced, metastatic prostate cancer, which in turn will improve clinical management of the disease.
2013 PCF China Young Investigator in Honor of Stanley Zax
Lu Yang, MD
West China Hospital, Sichuan University
Mentors: Qiang Wei, MD and Tianyong Fan, MD
Project Title: Treating inflammation to prevent prostate cancer initiation and progression.
Description:
- Growing evidence points to a link between inflammation and the initiation of prostate cancer. It is also linked to the progression of prostate cancer to being resistant to treatment.
- Dr. Yang and his team will conduct four Phase 1 clinical studies to investigate the effects of anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs), like aspirin, on prostate tumor initiation and progression.
- His team will also outline the precise molecular mechanism behind the effects of anti-inflammatory agents on preventing disease progression.
What this means to patients: The use of non-steroidal, anti-inflamatory drugs may provide a new treatment to prevent prostate cancer initiation and progression.
2013 LeFrak Family-PCF Young Investigator Award
Ardeshir Rastinehad, DO
Icahn School of Medicine at Mount Sinai Hospital
Mentor: Ashutosh Tewari, MD
Proposal Title: High Resolution MRI/ Multiphoton Microscopy (MPM) Ex Vivo Imaging Studies of Prostatic and Peri-Prostatic Tissue
Description:
- Evaluation of surgically removed prostate tissues allows surgeons to determine the extent of disease and the success of surgery in removing all affected parts. Currently this is done by evaluating tissue slices under the microscope (histopathology). New methods to improve tumor detection in prostatectomy samples will improve patient management.
- Ardeshir Rastinehad is evaluating the efficacy of molecular imaging techniques for evaluating post-surgical prostatectomy specimens for the presence of prostate cancer.
- High resolution Magnetic Resonance Imaging (MRI) and Multi-Photon Microscopy (MPM) will be used to evaluate freshly removed prostatectomy specimens and construct a 3D image of the prostate. The presence and location of tumors and the extent of invasion will be determined and compared with findings from gold-standard histopathology techniques.
- If successful, this project will credential novel imaging-based techniques for identifying and characterizing prostate cancer in prostatectomy samples and will create an atlas of prostate images that can be used to make treatment decisions and train urologists and pathologists in patient care.
What this means for patients: New techniques to identify and characterize prostate tumors will lead to improvements in patient staging and management. Dr. Rastinehad is evaluating the utility of molecular imaging techniques for mapping prostate cancer in prostatectomy samples. This will lead to improved disease staging and enable the creation of more optimal treatment plans for patients.