Human conventional renal cell carcinoma (CCC) remains resistant to current therapies. Focal Adhesion Kinase (FAK) is upregulated in many epithelial tumors and clearly implicated in nearly all facets of cancer. However, only few reports have assessed whether FAK may be associated with renal tumorigenesis. In this study, we investigated the potential role of FAK in the growth of human CCC using a panel of CCC cell lines expressing or not the von Hippel‐Lindau (VHL) tumor suppressor gene as well as normal/tumoral renal tissue pairs. FAK was found constitutively expressed in human CCC both in culture cells and freshly harvested tumors obtained from patients. We showed that CCC cell growth was dramatically reduced in FAK‐depleted cells or after FAK inhibition with various inhibitors and this effect was obtained through inhibition of cell proliferation and induction of cell apoptosis. Additionally, our results indicated that FAK knockdown decreased CCC cell migration and invasion. More importantly, depletion or pharmacological inhibition of FAK substantially inhibited tumor growth in vivo. Interestingly, investigations of the molecular mechanism revealed loss of FAK phosphorylation during renal tumorigenesis impacting multiple signaling pathways. Taken together, our findings reveal a previously uncharacterized role of FAK in CCC whereby FAK exerts oncogenic properties through a non canonical signaling pathway involving its scaffolding kinase‐independent properties. Therefore, targeting the FAK scaffold may represent a promising approach for developing innovative and highly specific therapies in human CCC.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Hervé Lang1, Claire Béraud2, Audrey Bethry2, Sabrina Danilin3, Véronique Lindner4, Catherine Coquard3, Sylvie Rothhut3, Thierry Massfelder3 1Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Department of Urology, Strasbourg, 67091 France 2UROLEAD SAS, School of Medicine, Strasbourg, 67085 France 3INSERM U1113, Section of Cell Signalisation and Communication in Kidney and Prostate Cancer, University of Strasbourg, School of Medicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67085 France 4Hôpitaux Universitaires de Strasbourg, Hôpital de Strasbourg-Hautepierre, Department of Pathology, Strasbourg, 67200 France Correspondence to: Thierry Massfelder, email: massfeld@unistra.fr Keywords: renal cell carcinoma, human tumors, patient-derived xenograft models Abbreviations: CCC, clear cell renal cell carcinoma; PDX, patient-derived tumor xenograft; VHL, von Hippel-Lindau tumor suppressor gene Received: September 08, 2015 Accepted: July 05, 2016 Published: July 18, 2016

Renal-cell carcinoma (RCC) accounts for 2% of cancer diagnoses and deaths worldwide. Clear-cell RCCs represent the vast majority (85%) of kidney cancers and are considered morphologically and genetically as immunogenic tumors. Indeed, the RCC tumoral microenvironment comprises T cells and myeloid cells in an immunosuppressive state, providing an opportunity to restore their activity through immunotherapy. Standard first-line systemic treatment for metastatic patients includes immune-checkpoint inhibitors (ICIs) targeting PD1, in combination with either another ICI or with antiangiogenic targeted therapy. During the past few years, several combinations have been approved with an overall survival benefit and overall response rate that depend on the combination. Interestingly, some patients achieve prolonged complete responses, raising the question of whether these metastatic RCC patients can be cured. This review will focus on recent therapeutic advances in RCC and the clinical and biological aspects underpinning the potential for healing.

Polydiacetylenic nanofibers (PDA-Nfs) obtained by photopolymerization of surfactant 1 were optimized for intracellular delivery of small interfering RNAs (siRNAs). PDA-Nfs/siRNA complexes efficiently silenced the oncogene Lim-1 in the renal cancer cells 786-O in vitro. Intraperitoneal injection of PDA-Nfs/siLim1 downregulated Lim-1 in subcutaneous tumor xenografts obtained with 786-O cells in nude mice. Thus, PDA-Nfs represent an innovative system for in vivo delivery of siRNAs.

Prostate cancer is one of the most common diseases among men worldwide and continues to pose a serious threat to health. This review shows the history and the new developments in the management of prostate cancer, with an emphasis on a range of therapeutic approaches, such as hormone therapy, radiation therapy, surgery, and innovative targeted therapeutics. The evolution of these treatments is examined in light of clinical outcomes, patient quality of life, and emerging resistance mechanisms, such as the recently shown vitamin D-based strategies. New developments that have the potential to increase survival rates and reduce side effects are also discussed, including PARP inhibitors (PARPis), immunotherapy, and tailored medication. Additionally, the use of biomarkers and sophisticated imaging methods in therapeutic decision-making is explored, with a focus on how these tools might improve patient care. The absolute necessity for a multidisciplinary approach for improving treatment strategies is becoming more and more apparent as our understanding of the biology of prostate cancer deepens. This approach ensures that patients receive customized medicines that fit their unique profiles. Future avenues of investigation will focus on resolving issues dealing with treatment efficacy and resistance to improve treatment results, ultimately leading to disease cure for prostate cancer patients.