Career Enhancement Program (CEP)

Labros Meimetis, PhD – Research Assistant Professor of Radiology

Project Title: Tumor Targeted RadioVaccination for Heterogeneous Metastatic Castration Resistant Prostate Cancer

Description:  Currently, there is no treatment that can cure patients with metastatic castration resistant prostate cancer (mCRPC).

The reason for this is that mCRPC tumors contains cancer cells with different response rates to treatment. Unfortunately, most standard of care cancer drugs are designed to kill single cell types by disrupting specific receptors, enzymes, or cellular division. Thus, even small populations of cancer cells in a tumor that are not susceptible to a drug’s mechanism of action, will evade cell death and continue growing after treatment.

To better address the treatment challenges of mCRPC, we have designed a new drug paradigm called RadioIMmunoStimulants (RIMS). RIMS accomplishes this by utilizing a therapeutic radiometal that can kill target and non-target cancer cells and combines it with an immunostimulant payload, all in one tumor targeted compound. Success in this program will lead to future clinical trials of a novel precision immunotherapy to improve the lives of patients living with mCRPC.

Quaovi Sodji, MD, PhD – Assistant Professor of Human Oncology

Project Title: Design and characterization of virus-free CRISPR-CAR T cells targeting STEAP1 for allogeneic CAR T cell therapy against metastatic castration-resistant prostate cancer

Description:  When prostate cancer spreads and becomes resistant to traditional hormone therapy, it is known as metastatic castration-resistant prostate cancer (mCRPC). This stage is particularly challenging to treat, and new therapies are urgently needed.

One promising approach involves using chimeric antigen receptor (CAR) T cells, which are engineered to better recognize and attack cancer cells. We propose a CAR T cell therapy that targets a protein called STEAP1, found in 80% of mCRPC cases but not in normal tissue outside of the prostate.

By using CRISPR-Cas9 gene-editing techniques, these CAR T cells will be designed to avoid causing harmful immune reactions and to counteract the cancer’s ability to suppress the immune system. Additional modifications will also be made to produce an “off-the-shelf” universal CAR T cell therapy that could be used for any patient with mCRPC, potentially offering a powerful new treatment option.

Irene Ong, PhD – Associate Professor of Obstetrics & Gynecology

Project Title: Computational Methods for Multi-omic Data Analysis to Enhance Prostate Cancer Research

Description:  Prostate cancer is a complex disease influenced by numerous genetic and environmental factors. Many prostate cancers can contain multiple lesions, any one of which may cause disease progression even after treatment. By collecting, integrating, and analyzing data from multiple sources (“multi-omics”) and by developing novel tools that can account for data from multiple lesions per patient, previously undiscovered biomarkers and pathways can be identified. These newly discovered relationships can guide future clinical trials and assist with the development of future treatments.

John Floberg, MD, PhD – Assistant Professor of Human Oncology

Project Title: Imaging and Circulating Biomarkers for Early Identification of Treatment Response and Resistance in Neuroendocrine Prostate Cancer Treated with Targeted Radiopharmaceutical Therapies

Description:  Neuroendocrine prostate cancer is an aggressive form of prostate cancer with a poor prognosis and limited treatment options. A potential novel treatment approach for these cancers is to us a drug targeted specifically to a molecule expressed by these cancer cells labeled with a radioactive isotope. The radioactive isotope is then able to deliver radiation therapy targeted directly to the cancer. While such a treatment shows much, it is complicated to give, expensive, there are safety concerns when giving it, and it may still be an ineffective treatment for these patients whose cancers progress rapidly. This proposal aims to test tools that will help identify patients who are most appropriate for this treatment, and to identify response and resistance to this drug early in the course of therapy. We specifically propose to test two potential tools. The first is a tool that automatically looks at the response of each area of cancer within the body by comparing an image taken before therapy began and an image taken mid-way through the treatment course. The second tool identifies cancer cells circulating freely within the patient’s blood. If the work in this proposal demonstrates that these tools can identify patients best suited for this targeted radioisotope therapy, we could offer better personalized cancer care to ensure they are receiving an appropriate and effective therapy.  

Ali Pirasteh, MD – Assistant Professor of Radiology

Project Title: Novel FAP-targeted Approach to Metastatic Prostate Cancer

Description:  The recent development of prostate-specific membrane antigen (PSMA)-directed imaging and therapy has made a significant impact on the lives of prostate cancer patients, mainly through (1) detection of cancer that was previously not seen until further advanced, and (2) by prolonging survival in patients with advanced disease through PSMA-targeted therapies. The vast majority of patients with advanced prostate cancer relapse after initial favorable response to PSMA-targeted therapies. On average, these therapies prolong life by 4 months. Hence, novel diagnostic and therapeutic approaches that complement the current methods are needed to enhance the treatment of advanced prostate cancer. Fibroblast activation protein (FAP) is a molecule found in aggressive prostate cancer tumors. Preliminary research studies support that by targeting FAP, there is potential for the detection and treatment of prostate cancer. This proposal will demonstrate that FAP can be used as a target to detect prostate cancer, and that FAP can become a target for future therapies. Successful completion of this research proposal will justify future larger research studies to demonstrate that FAP-targeting diagnostic tools and therapies can make a difference in the lives of patients with advanced prostate cancer. 

Anthony Serritella, MD – Assistant Professor of Hematology, Medical Oncology and Palliative Care

Project Title: Utilizing liquid biopsy in metastatic prostate cancer to recognize lineage plasticity and develop new therapies (MORPH)

Description:  Metastatic prostate cancer is a deadly disease that resists treatment by transforming its identity to behave less like prostate cancer and more like other forms of cancer (such as small cell lung cancer). This transformation makes the cancer challenging to diagnose and even more difficult to treat. Neuroendocrine prostate cancer is one particularly aggressive form of prostate cancer that has undergone transformation.

We plan next generation analyses on tumor cells that are shed from the patient’s tumor that circulates in the blood stream (i.e. liquid biopsies). We are particularly interested in how the proteins expressed on a tumor cell’s surface change over time. Analysis of these surface genes and proteins will elucidate which treatments are best suited for a patient and what future treatments could be explored in future clinical trials.

Through examining how these cancers are similar and may respond to treatment in a similar manner, we hope to develop better treatments for lethal prostate cancer.

Jordan Slagowski, PhD, DABR – Assistant Professor of Human Oncology

Project Title: Targeting intraprostatic lesions in HDR brachytherapy: A unified approach with sparse optimization, deep learning, and multi-modal imaging

Description:  Recent advancements in molecular imaging techniques present new opportunities to visualize regions of high cancer burden that could be used to treat aggressive forms of prostate cancer more effectively. Brachytherapy is a highly effective form of radiation therapy where a radioactive source is implanted directly in the tumor which helps spare nearby healthy tissues to reduce side effects. However, two major limitations exist in the current paradigm. Intraprostatic lesions identified from MRI and PET images are not visible on ultrasound and catheters are placed based on physician intuition and experience which increases variability and is suboptimal. This proposal aims to develop a novel platform that will directly integrate 3D imaging information with live ultrasound and provide physicians with real-time recommendations of where to insert needle catheters during brachytherapy procedures using artificial intelligence. By providing physicians with dynamic, data-driven recommendations for needle catheter insertion during brachytherapy procedures, we aim to achieve highly conformal, biology-driven, personalized radiation treatments.

Marina Sharifi, MD, PhD – Assistant Professor of Hematology, Medical Oncology, and Palliative Care

Project Title: Interrogating the molecular signatures of Aggressive Variant Prostate Cancer via longitudinal liquid biopsy

Description:  Prostate cancers start out highly dependent on hormone signaling from androgens such as testosterone. A type of medication called androgen signaling inhibitors (ASIs) which block androgen hormone signaling are a very effective treatment for most men with metastatic prostate cancer. About one out of five metastatic prostate cancers develop resistance to ASI. Once this transition occurs, the cancer becomes aggressive with limited effective treatments. The challenges in accurately identifying when this transition occurs in patients has also been a barrier.  

To address this need for better ways to identify and understand the transition to androgen independent aggressive disease (AVPC), we leveraged a large dataset of RNA level profiling of metastatic prostate cancer tissue samples with known clinical outcomes that allows us to look beyond DNA changes into broad signaling pathway patterns that give insight into prostate cancer cell behavior. We think that this pattern, a type of molecular signature, will be a more sensitive and specific way to identify AVPC than what was previously available.  

To utilize this molecular signature to understand how, why and when prostate cancers transition to AVPC, we developed a platform to identify our AVPC molecular signature in cancer cells from the blood of patients with metastatic prostate cancer, which we have tested successfully in a small pilot cohort of metastatic prostate cancer patients. 

The goal is to (1) test our liquid biopsy platform in a larger cohort of patients with metastatic prostate cancer to understand how often we see the AVPC molecular signature when patients develop ASI resistance, see if we can detect the AVPC signature emerging before clinical ASI resistance is identified, and to understand the characteristics of tumor cells with the AVPC signature in the blood and (2) to understand whether targeting this pathway may be an effective strategy in AVPC. 

Grace Blitzer, MD – Assistant Professor of Human Oncology

Project Title: The role of ctDNA and CTCs in guiding initiation of salvage radiation therapy

Description:  Prostate cancer is the most common cancer in men, and is often treated by surgery. However, in 20-50% of cases, prostate cancer can recur after surgery. When this happens salvage radiation is used to treat the prostate cancer – but only cures the cancer in approximately 50% of men. One of the reasons for this low cure rate could be the lack of clear guidance on when patients should get radiation. Our proposal is investigating a blood test to help identify when men with recurrent prostate cancer after surgery should get radiation therapy. This blood test examines both the DNA and intact cancer cells in a patient’s blood. We first need to run a pilot clinical trial to determine if this blood test can accurately detect prostate cancer, and help predict how aggressive the cancer will be. Ultimately, we plan to use this blood test to run national clinical trials personalizing treatments for men with recurrent prostate cancer.