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Prostate cancer is now the most common non-cutaneous cancer among men in Ireland. Most prostate cancer patients are cured by local-regional treatment, in which radiotherapy has a prominent role when used as a single modality or in combination with androgen deprivation therapy. Despite intensive radiation therapy treatment, disease recurrence will occur in up 30-50% of patients, especially those with high-risk disease. Determining which patients are at a greater risk of relapse after treatment poses a significant dilemma for the clinician. For this reason, high-risk prostate cancer is an appropriate disease to pursue novel biomarkers that enable the prediction of response to radiation therapy. Traditionally, a blood test (PSA or prostate specific antigen), clinical examination, assessment of tumour pathology are the principal diagnostic and treatment decision-making tools. However this approach is not able to identify the presence of a prostate cancer that is radioresistant and may not respond to radiotherapy. In this study we are therefore examining a new way of detecting those patients with radioresistant tumours. The aim of this study is to investigate novel genetic markers, called miRNAs, whose presence may be associated with a greater risk of prostate cancer recurring after radiotherapy. We will assess the contributions of key miRNAs to radioresistance by determining their effects on altering cell sensitivity to radiation. Importantly, we will also assess the importance of the radioresistance-associated miRNAs in pre-treatment tumour samples from patients. Ultimately an improved understanding the mechanisms and identifying cellular features predictive of radioresistance will aid clinicians detecting the patients at high risk of radiation therapy failure, ultimately improving treatment efficacy and patient survival.
Despite intensive radiation therapy treatment, recurrence will occur in up 30-50% of prostate cancer patients. Determining which patients are at greater risk of relapse after treatment poses a significant dilemma for the clinician, and the identification of novel markers that enable prediction of response to radiation therapy is required. This project aims to identify genetic markers called miRNAs which may be used as predictors of resistance to radiotherapy in prostate cancer patients.
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