Research: 2018 – London

Project Title:
Pre-clinical optimization and assessment of a novel blood-based circulating tumor cell (CTC) assay to differentiate between indolent versus aggressive disease.
Investigators:
Dr. Alison Allan, Cancer Research Laboratories Program, London Regional Cancer Program, London Health Sciences Centre; and Lawson Health Research Institute
 
Dr. Alison Allan is a Senior Oncology Scientist in the London Regional Cancer Program at London Health Sciences Centre and an Associate Professor in the Departments of Anatomy & Cell Biology and Oncology at Western University. Dr. Allan is a previous recipient of a Canadian Institutes of Health Research (CIHR) New Investigator Award (2010-2015) and an Early Researcher Award from the Province of Ontario (2010-2015). Dr. Allan’s translational research program is focused on cellular and molecular mechanisms of cancer metastasis; in particular the study of circulating tumor cells (CTCs) and how the knowledge gained from experimental studies in these areas can be translated to the clinic to benefit patients. Dr. Allan has published more than 53 peer-reviewed publications and her work has been cited more than 3,400 times. Most relevant to this project, Dr. Allan is a Canadian leader in the area of CTC analysis and technology development, and her research group is actively involved in several collaborative local and national/international multi-centre cancer clinical trials. As an example, Dr. Allan’s previous funding from RFD/PCFF contributed to an important multi-centre international clinical study between Memorial Sloan Kettering [PI; H. Scher], the Royal Marsden [Co-PI; G. Attard] and the London Health Sciences Centre (LHSC) [Co-PI; A. Allan]. This study demonstrates that an innovative CTC test developed by Epic Sciences can be used as a predictive biomarker to determine whether patients with metastatic CRPC are more likely to respond to targeted therapies (enzalutamide or abiraterone) versus chemotherapy. This is a potentially practice-changing study and an FDA biomarker submission is in preparation. Results of the study were published in the journal JAMA Oncology, and was listed as #6 on JAMA Oncology’s “Most Talked About Articles of 2018”; and #7 on the Prostate Cancer Foundation’s “Top 25 Provocative Papers of 2018”.
Project Abstract:
For many men, prostate cancer is diagnosed when it is slow-growing or indolent, and outcome of these patients is often very good. However, for other men with aggressive disease, prognosis is poor. This is primarily due to metastasis, which occurs when tumor cells spread from the prostate to other organs in the body. Therefore, one of the major clinical challenges in prostate cancer is differentiating between those patients who will have indolent versus aggressive prostate cancer in order to ensure that the most appropriate/effective treatment is provided. Research in the Allan lab focuses on developing tests that identify circulating tumor cells (CTCs) in a patient’s blood as a biomarker of aggressiveness and/or metastasis. Their recent work has been focused on advanced castrate resistant prostate cancer (CRPC), with excellent success. However, Dr. Allan and her team believe that CTC tests that can help differentiate between slow-growing versus aggressive prostate cancer should also be developed. The goal of this proposal is evaluate a new CTC assay called VyCAP using pre-clinical mouse models that have been engineered to have either slow-growing or aggressive prostate cancer. Successful completion of this study will allow this CTC test to move into early clinical studies to test its effectiveness in patients.
Scientific Abstract:
A major clinical challenge in prostate cancer (PCa) is differentiating between patients who have indolent versus aggressive disease. Metastasis causes most PCa deaths and has been associated with circulating tumor cells (CTCs) in the blood, which can be used to evaluate disease progression and/or response to treatment. We have recently contributed to the development/validation of a new CTC test for castrate resistant PCa that can predict which men will respond to androgen-targeted therapies versus taxanes. In this proposal we will apply our expertise to the question of differentiating indolent versus aggressive PCa through pre-clinical assessment of a new CTC assay called VyCAP. We have previously engineered PC-3 cells to knockout expression of Zeb1, resulting in significantly reduced growth, migration, and overall aggressiveness to control PC-3 cells. In this study, PC3Zeb- cells (slow-growing) or PC3control (aggressive) cells will be orthotopically injected into mice and blood samples will be collected. Blood from slow-growing versus aggressive models will be analyzed using the VyCAP assay and compared to measures of disease progression and metastasis. Successful completion of this study will allow us to evaluate the VyCAP assay in early clinical studies to test its effectiveness in differentiating indolent versus aggressive PCa in patients.
Impact on prostate cancer patients:
As described above, this project is a pre-clinical study that will lay the groundwork for moving to future patient studies. If the VyCAP test proves to be effective for differentiating between indolent versus aggressive disease in prostate patients, it can be used in the future by prostate cancer patients and their physicians to allow more informed decisions about treatment; hopefully preventing or reducing both overtreatment and undertreatment to ensure the best outcomes and quality of life.