About this Research Topic
The mammalian target of rapamycin (mTOR) as well as extracellular signal-regulated kinases (ERKs) are protein kinases that regulate signaling pathways involved in cellular metabolism, proliferation and differentiation. Both mTOR and ERK are serine-threonine kinases that represent a central point for the regulation of different biological processes including cell cycle, apoptosis, autophagy and protein synthesis. ERK kinases belong to the mitogen-activated protein kinases (MAPK) while mTOR is associated with the phosphoinositide 3-kinase (PI3K) kinase family. The dysregulation of mTOR and ERK signaling leads to the development of different diseases including cancer. In kidney carcinoma, inactivation of the VHL gene induces hyperactivation of the hypoxia-inducible factor (HIF), increasing the activity of ERK, mTOR and NF-κB signalling pathways that, in turn, contribute to cancer progression.
Renal cell carcinoma (RCC) is the most common kidney cancer representing about 3% of all types of human tumors. One third of RCC subjects develop metastases that are difficult to treat causing high mortality in RCC patients. The main treatment for patients with metastatic RCC is represented by the use of tyrosine kinase inhibitors (TKIs) and mTOR blockers. However, the treatment of advanced RCC with these inhibitors has shown limited success, since RCC patients develop resistance to cancer therapy. Many signaling pathways are dysregulated in RCC, including mTOR and ERK kinases that modulate cell proliferation, migration, apoptosis, autophagy and other biological processes, contributing to cancer progression. The goal of this research field is the study of molecules involved in kidney cancer, in particular, mTOR and ERK signalling pathways as well as possible new players, that may form a cancer network in RCC. The discovery of new elements associated with RCC could lead to the detection of new therapeutic targets for RCC treatment that could improve the overall survival and quality of life of metastatic RCC patients.
The aim of this Research Topic is to highlight significant scientific improvements in the research addressed to investigate the role of mTOR and ERK kinases in RCC. We welcome Original Research, Reviews, Methods and Opinion articles on the following topics:
• mTOR and ERK signaling in RCC development and progression
• mTOR and ERK function in cell growth and migration
• Autophagy and RCC: role of mTOR
• mTOR, ERK and HIF network for cell cycle and apoptosis regulation
• Targeting of signaling pathways driven by mTOR and ERK for RCC treatment
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