Expertise and collaboration – that's what it takes to connect laboratory breakthroughs to the clinic to benefit patients. At Sunnybrook's Odette Cancer Centre and Sunnybrook Research Institute, clinicians and scientists are especially proud of their leading translational research to further tailor cancer treatment for the individual.
Dr. Arun Seth and Dr. Robert Nam collaborate and share expertise to better detect prostate cancer, risk of aggressive prostate cancer, and to better differentiate recurrence risk for patients previously treated with surgery.
Dr. Seth is a cancer biologist, the director of molecular diagnostics in anatomic pathology and director of the genomics centre at Sunnybrook, and has over 20 years' of expertise in molecular oncology. Dr. Nam is a urologic oncologist, highly skilled surgeon and the head of the Genitourinary Cancer Care team at Sunnybrook's Odette Cancer Centre. Both are also scientists at the Sunnybrook Research Institute.
These researchers were the first to show that the expression or activation of a fusion gene known as TMPRSS2:ERG is a strong predictor of recurrence for patients previously treated with surgery. "TMPRSS2:ERG status helps identify patients at higher risk of disease progression," says Dr. Nam. "For example, a patient with low-grade cancer but fusion-gene positive would be at high risk of disease progression and we would need to treat him further. A patient with high-grade cancer and fusion-gene negative would be at low risk of recurrence and not need more treatment. The result would be more aggressive treatment for patients who really needed it, and no overtreatment for others at low risk,"
Says Dr. Seth, "Our findings pave the way for targeted therapies. Like the small molecule drug that blocks the production of abnormal cells in patients with chronic myeloid leukemia, similar interventions can be developed to inhibit prostate cancer cell growth at the molecular level in patients with TMPRSS2:ERG fusion-gene positive status."
Their study of 165 patients who underwent surgery showed 50 per cent of these patients had tumours with TMPRSS2:ERG expression. Of that group, 81 per cent experienced recurrence over a five-year follow-up. Nam and Seth are validating this finding in a larger study of 1,700 patients. To date, findings are consistent.
Another area of interest for Drs. Seth and Nam is to explore the potential for using expression of the TMPRSS2-ERG gene fusion to identify circulating prostate tumor cells (CTCs) in blood, which may be an indicator of possible metastases or cancer growth. This would be a simple and non-invasive way of evaluating a tumour's metastatic potential, and could be used to monitor the effectiveness of a patient's drug therapy.
In the longer term, Nam and Seth hope to potentially use fusion gene status as an improved marker for overall prostate cancer screening. Currently, men are screened using the PSA test (prostate specific antigen). Diagnosis is confirmed by a biopsy. TMPRSS2:ERG has been shown to be activated only in cancer cells and Nam and Seth envision the strong possibility of fusion gene status to detect prostate cancer through non-invasive tests such as blood or urine tests. Dr. Seth's lab has already been successful in detecting the expression of the gene in preliminary blood testing with 20 patients.
Dr. Seth says, "Rob and I hope to develop a newer, more objective biomarker gene test somewhat similar to the Oncotype DX assay for risk of progression in some breast cancers." Dr. Nam adds, "Our continued collaborations will help better tailor treatment for the individual prostate cancer patient."