Development of patient-derived prostate cancer cells for early prediction of therapy response
Stanley Liu, MD, PhD, Sunnybrook-Odette Cancer Centre
Dr Michelle Downes
Dr Michelle Downes
Lead Investigator Bio:
Dr.Stanley Liu performed his PhD, MD and residency in Radiation Oncology at the University of Toronto, followed by post-doctoral fellowship studies at the Gray Institute, University of Oxford, UK. He is a clinician-scientist (Radiation Oncologist and Scientist) at the Sunnybrook-Odette Cancer Centre who has treated prostate cancer patients in the GU site since 2014. He runs a translational research lab at Sunnybrook Research Institute where he oversees graduate students, residents and technicians who are all focused on improving outcomes for prostate cancer patients by researching mechanisms of treatment resistance. He manages the Odette Cancer Centre GU biobank which collects patient biofluids and biopsy samples to facilitate translational research studies. His previously funded research from Ride for Dad has demonstrated that: 1- microRNA in preclinical prostate cancer models can promote radioresistance and aggression; 2- microRNA in the urine (post-DRE) or blood are promising non-invasive biomarkers that can stratify patients according to risk status.
Men with newly diagnosed metastatic prostate cancer have traditionally been treated with hormone therapy alone. New evidence indicates that adding chemotherapy or newer generation hormone therapies can extend the survival of these men. However, these treatments can cause considerable toxicity and there is currently no means to predict which of these treatments would be most effective for a patient’s cancer. We believe that by growing and treating a patient’s own prostate cancer cells in the lab, we will be able to predict which treatment will be most effective to use for that patient in the clinic. We have been able to successfully biopsy and grow a patient’s cancer cells in our lab and measure their response to various treatments. We are proposing to establish proof-of-principle in a group of prostate cancer patients and correlate the treatment response of their cancer cells in the lab with their actual response in the clinic. This may allow us to better tailor treatments for prostate cancer patients in the future.
Background/clinical problem: Incorporation of systemic therapies (androgen receptor axis inhibitors or chemotherapy) improves survival of metastatic hormone-sensitive prostate cancer patients (met HSPCa). Prostate radiotherapy has recently been demonstrated to improve overall survival in limited/oligometastastic PCa. However, no data clearly support the use of one therapy over another, and therapy decisions are largely based upon perceived treatment toxicity and extent of metastatic disease. We urgently need approaches that will predict which therapies patients will respond to best. Objective: To derive patient-derived prostate cancer cells (PDCs) from met HSPCa patients and correlate their in vitro treatment responses with their clinical responses. Methods: We will cultivate PDCs from oligometastatic hormone-sensitive PCa (n=20) and determine IC50 values for systemic treatments and SF2 for radiotherapy in vitro and correlate these values with RECIST and PSA response in these patients. Outcomes: The prediction of systemic and radiotherapy response in met PCa will improve patient outcomes by allowing oncologists to select therapies that have greater predicted efficacy, thereby enhancing the therapeutic ratio. This proof-of-principle research may establish the potential of PDCs as a rapid and effective means to advance personalized medicine in prostate cancer which currently remains a significant clinical hurdle.
Impact on prostate cancer patients:
The prediction of systemic and radiotherapy response in prostate cancer patients will improve patient outcomes by allowing oncologists to select therapies that have greater predicted efficacy, thereby enhancing the therapeutic ratio. This proof-of-principle research may establish the potential of PDCs as a rapid and effective means to advance personalized medicine in prostate cancer which currently remains a significant clinical hurdle. Additionally, for patients who have exceptional clinical responses (or conversely, poor clinical responses), we would be able to leverage their PDCs to investigate the underlying biological causes in future genomic and molecular studies. Equally important, this research will support the training of a translational prostate cancer PhD researcher and enhance future capacity in prostate cancer research.