Over the years, an emphasis has been placed on the management of prostate cancer with radiotherapy (RT) dose escalation, fractionation, use and length of androgen deprivation therapy (ADT), tissue, blood, and imaging markers of outcome, and small molecule/gene/viral vector targeted therapy. Some current projects include:
1) Enhancement of Prostate Cancer Identification and Targeting Via Quantitative Imaging
In collaboration with a team of investigators that include Radka Stoyanova, Ph.D., Sanoj Punnen, M.D, Matthew Abramowitz, M.D., Merce Jorda, M.D., Ph.D., Oleksandr Kryvenko, M.D., software has been developed to analyze prostate multiparametric MRI images to identify and risk classify regions of interest suspicious for cancer automatically. Each prostate image sequence is fused together and analyzed on a pixel by pixel basis to identify clusters of pixels that define suspicious regions (habitats) that deserve attention. Traditional image classification methods (PI-RADS) have ignored this quantitative information. A Habitat Risk Score (HRS) method has been developed, with preliminary data showing that incorporating radiomics, radiogenomics, and deep learning enhance the predictive value.
In addition, three on-going clinical trials serve as the platforms for these imaging and additional biomarker studies. The trials include, the MAST trial (PI: Punnen), the CoMBINe Trial (PI: Pollack), and the BLaStM Trial (PI: Pollack).
2) Circulating Tumor Cells (CTCs) in Patients Treated with Radiotherapy.
In collaboration with Brian Marples, Ph.D., and Richard Cote, M.D., CTCs are being quantified in patients enrolled in the clinical trials mentioned above. There has been little published on CTCs in men managed with active surveillance, prostatectomy or radiotherapy. In addition to quantification, we have developed methods to isolate single cells for transcriptomic analysis in collaboration with Sion Williams, Ph.D., who leads the Oncogenomics core. Moreover, we have established over 20 PDX models from patients enrolled in radiation treatment trials and referencing the transcriptomic profiles of such PDXs to that of the patient CTCs and patient habitat directed prostate biopsies.
3) Heterogeneity and Prostate Cancer Outcomes.
In collaboration with Erin Kobetz-Kerman, Ph.D., we have reported that certain Hispanic/Latino ancestral subgroups have a very high risk of prostate cancer specific mortality. This work is being expanded to look at patient reported and genetic ancestry markers in men treated with radiotherapy.
4) Oncolytic Viral Therapy of Prostate Cancer
In collaboration with Glen Barber, Ph.D., we have found in preliminary studies that a replication competent Vesicular Stomatitis Virus (VSV) vector loaded with interferon-Î² (IFNÎ²) is highly efficacious when combined with radiotherapy for the treatment of prostate cancer in mouse models. The combined treatment cured 100% of mice with prostate cancer. Using a syngeneic model, such cured mice remained tumor free when rechallenged with tumor cells; only mice treated to knock down CD8+ cells were able to form tumors. The next step is to see if this can be applied very high risk patients treated with radiotherapy.
5) Development of Multifunctional Nanoparticles to Image and Treat Prostate Cancer.
In collaboration with Brian Marples, Ph.D., Yidong Yang, Ph.D., and Shanta Dhar, Ph.D., we are developing novel prostate cancer directed nanocarriers loaded with antineoplastic chemotherapy and targeted agents to be combined with radiotherapy. As a proof of principle, nanocarriers loaded with shRNA against MDM2 and linked to anti-PSMA antibody were found to efficiently knock down MDM2 in vitro and in vivo in preliminary studies.