Researchers from 91社区鈥檚听听(VPDIGM) and clinicians from 91社区 Health Centre (MUHC) are stepping up efforts in the fight against clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer, by seeking to discover improved methods for risk assessment and therapeutic treatment.听
The two projects, one devoted to establishing prognosis biomarkers, and another for treatment development, are funded by the US Department of Defense (DoD) to the tune of nearly $2M.听
More than 400,000 people are diagnosed with kidney cancer each year globally, including 8,100 in Canada and 81,800 in the US. Renal cell carcinoma is the most common form of kidney tumours, with ccRCC accounting for 75-80% of RCCs. Research shows the main risk factors for developing ccRCC include smoking, obesity and hypertension. It has also been strongly linked to military service, through the consumption of contaminated drinking water, and exposure to chemical solvents and heavy metals.听
Patients who present with the localized disease, when the tumour is confined to the kidneys, undergo nephrectomy through which the tumour or affected kidney is removed during the surgery. However, 30-40% of these patients experience disease recurrence. There is no biological marker in routine clinical practice to identify patients who are at high risk for disease recurrence to act early enough to prevent the relapse or treat it before it spreads.听
鈥淭he goal of our study supported by the Translational Research Partnership Award is to develop a new prognostic algorithm which combines genetic information of tumours and clinical annotations, to be used by clinicians in order to estimate the risk of the disease relapse,鈥� Yasser Riazalhosseini, PhD, Associate Professor of Human Genetics, and head of cancer genomics at VPDIGM, points out.听听听
鈥淥utcomes of this study will allow accurate risk stratification for recurrence/progression, timely identification of patients with failure, better adapted follow-up regimens, and potentially better selection of patients for adjuvant treatments,鈥� adds Prof. Riazalhosseini.听
There is a growing population of patients, including veterans (men and women), who suffer from metastatic and relapsed ccRCCs. Clear cell renal cell carcinoma is the most aggressive and the most common form of kidney cancer. 鈥淭his type usually ends up in metastatic form. The brain is one of the target organs of metastasis. But these tumours occur quite often in lungs and in bones. Our new algorithms will help in early detection,鈥� Prof. Riazalhosseini says.听
Treatment options for these patients are limited to drugs with anti-angiogenesis functions or immunotherapies that do not directly target cancer cells but rather other cells that are in contact with cancer cells in the tumour microenvironment.听
Of the many patients who are treated now with available drugs, a small fraction of them respond to treatments, but the majority do not, or they develop resistance to therapies. 鈥淭he new therapies that we hope to develop with the support of the Idea Development Award will be used to target tumours that show resistance to currently available treatments,鈥� Prof. Riazalhosseini says.听听
鈥淭he goal is to validate essential roles of a new biological pathway which was not previously connected to kidney cancer, in kidney cancer development. We want to understand how this pathway drives kidney cancer formation and relapse, and then use specific inhibitors that block functions of this pathway in tumour cells,鈥� adds Prof. Riazalhosseini. 鈥淭he goal here听is to understand the biology of the initiation of these kidney cancer tumours because researchers believe that there are a very specific set of cells that initiate RCC tumours and are responsible for the resistance of these tumours to treatments and their recurrence. This project aims to听understand the biology of these cells and use this information to develop new treatment approaches.鈥澨�
Prof.听 Riazalhosseini鈥檚 research team will start by defining and targeting cancer cell-intrinsic vulnerabilities in renal cell carcinoma in relation to metastatic ccRCC, which accounts for 30-40% of all cases, and which is currently incurable.听 鈥淭his proposed study will lead to the identification of key molecular targets, presenting an opportunity to focus our expertise to develop a new generation of therapeutic strategies that directly target cancer cells in ccRCC tumours.鈥澨�
The research awards directly support the multidisciplinary research program that Prof.听 Riazalhosseini and Simon Tanguay, MD, Chair of the Division of Urology at 91社区, have established to facilitate precision medicine in kidney cancer. These studies will address two major challenges in clinical management of RCC: accurate prognosis to prevent relapse and treating resistant tumours.听
鈥淲e focus on secondary prevention of kidney cancer in patients who underwent curative surgery through which the tumours are removed from the kidney. Our goal is to use genetic information of those tumours that were removed at surgery to predict the risk of relapse. Based on these predictions, clinicians can then apply personalized follow-up strategies to prevent a relapse. In addition, our research on target identification will lead to therapeutic innovations that result in new treatment strategies for patients with advanced or metastatic tumours,鈥� Prof. Riazalhosseini explains.听