mTOR inhibitor and bone-targeted drugs break the vicious cycle between clear-cell renal carcinoma and osteoclasts in an in vitro co-culture model

Publication date: Available online 27 February 2019Source: Journal of Bone OncologyAuthor(s): Chiara Spadazzi, Federica Recine, Laura Mercatali, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Alberto Bongiovanni, Valentina Fausti, Toni IbrahimAbstractThe skeleton is one of the most common sites of metastatic spread from advanced clear-cell renal carcinoma (ccRCC). Most of the bone lesions observed in RCC patients are classified as osteolytic, causing severe pain and morbidity due to pathological bone destruction. Nowadays, it is well known that cancer induced bone loss in lytic metastasis is caused by the triggering of a vicious cycle between cancer and bone resident cells that leads to an imbalance between bone formation and degradation. Targeting the mammalian target of rapamycin (mTOR) is an efficient treatment option for metastatic renal carcinoma patients. Moreover, bone targeted therapy could benefit bone metastatic cancer patients caused by advanced RCC. However, more data is needed to support the hypothesis of the beneficial effect of a combined therapy. The aim of this work is to investigate the effect of targeting mTOR and the sequential combination with bone targeted therapy as a strategy to break the vicious cycle between ccRCC cells and osteoclasts. A previously optimized fully human co-culture model is used to mimic the crosstalk between Caki-2 cells (ccRCC) and osteoclasts. Cells are treated at fixed timing with everolimus, zoledronic acid and denosum...
Source: Journal of Bone Oncology - Category: Cancer & Oncology Source Type: research