MicroRNAs (miRNAs) are emerging as promising molecules in the diagnosis, prognosis and treatment of urological tumours. Recently, our group performed two independent studies highlighting that miR-210-3p may represent a useful biomarker not only for diagnosis but also for post-surgery ccRCC management.
Starting from these results and with the aim to further assess the robustness of this miR-210-3p as a diagnostic and prognostic biomarker, we will analyze its levels in tissue, serum and urine specimens collected at surgery and during follow-up visits (from 3 to 12 months) from ccRCC disease-free patients and in patients presenting metastatic progression. Moreover, primary cell culture from tumor and metastatic tissues will be set up as relevant tool to explore the miR-210-3p contribution to ccRCC establishment and drug sensibility.
Research plan: i) evaluation of miR-210-3p expression levels in normal, primary tumor and metastatic tissues and in serum and urine collected at the day of surgery and during the follow-up of patients diagnosed with ccRCC, to clarify if clinical outcomes may correlate with its expression level; ii) evaluation of miR-210-3p contribution to ccRCC tumor phenotype and metastatic progression; iii) evaluation of the functional relevance of miR-210-3p in the response to conventional cytotoxic drugs treatments.
The comprehension of the contribution of miR-210-3p to ccRCC phenotype and metastatic progression may be relevant to pave the way for the identification and design of innovative clinical approaches in this tumor.
Nowadays most of kidney tumors are incidentally diagnosed. Among renal neoplastic diseases, ccRCC is the most common malignancy and its early diagnosis remains challenging. This is secondary to the fact that there are still not specific tools that allow identifying patients at risk for ccRCC in their clinical history. Furthermore, there is a lack of tools that can be used to accurately
understand the progression of this disease. Currently, no clinically validated biomarkers are available to aid the diagnosis, disease monitoring and treatment efficacy in ccRCC. Furthemore, in the last years, various targeted therapies have been approved for ccRCC.
Although these therapies have been shown to partially improve overall survival, disease progression is observed in a very high percentage of patients with advanced ccRCC. This research project aims at providing novel insights in the diagnosis, prognosis of ccRCC. In addition the project aims at evaluating whether multi-targeting anti-neoplastic approach shows efficacy in the treatment of
ccRCC-derived cells.
Under a clinical point of view, the availability of efficacious adjuvant therapies and a specific knowledge of patient¿s prognosis based on histological and molecular characterization, might induce even more surgeons to apply conservative treatments and nephron sparing surgery in subjects with ccRCC. An increased rate of patients eligible for nephron sparing surgery could further increase the
overall survival of patients suffering from ccRCC, and generally from kidney tumors. The combination of nephron sparing surgery and efficacious adjuvant pharmacological treatments could represent in the future the gold standard approach for patients with ccRCC. This consideration is based on the fact that also cytoreductive treatments significantly improve the survival of patients with metastatic ccRCC even in the targeted therapy era.
The advancement of knowledge in ccRCC biology, guaranteed by this project, will provide useful information for the understanding of ccRCC tumorigenesis and for the identification of innovative tools or targets to design novel therapeutic strategies. The identification of miR-210-3p contribution to ccRCC phenotype will provide the biological basis for the translation of this knowledge from bench to bedside. Furthermore, identification of potential biomarkers of diagnosis and responsiveness to the ccRCC targeted therapy, such as miR-210-3p found in tissue and also in the peripheral blood and/or urine of ccRCC patients may
provide insights into the biology of the tumor and the effects of therapeutic interventions. Finally, a biomarker such as a miRNA may contribute to the stratification of patients according to progression risk and to a better assessment of the risk / benefit drug administration. Indeed, miRNA can be considered optimal candidates as potential diagnostic biomarkers not only due to high level of stability in body fluids but also their ability to be easily assessed by routinely molecular methods.