Molecular Pathogenetics of Renal Cancer

Abstract

Recent developments in genetics and molecular biology have led to an increased understanding of the pathobiology of renal cancer. Thorough knowledge of the molecular pathways associated with renal cancer is a prerequisite for novel potential therapeutic interventions. Studies are ongoing to evaluate novel anticancer agents that target specific molecular entities. This article reviews current knowledge on the genetics and molecular pathogenesis of sporadic and inherited forms of renal cancer.

The prognostic value of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue markers in localized renal cell carcinoma: A retrospective study of tissue microarrays using immunohistochemistry

“…For several decades, clinicians have observed the limited accuracy and value of the currently used clinicopathological variables and have attempted to search for new specific molecular tissue biomarkers [6, 14]. This study found pS6 for CSS and RFS, and Ki-67 for OS, CSS, and RFS, as significant prognostic markers for survival among the nine selected tissue markers closely related to RCC oncogenesis and tumor progression (p<0.05, Table 3).…”

“…This high mortality rate for RCC is due to a lack of confirmed, efficacious therapeutic options for long-term tumor control. The difficulty in developing new treatment for RCC lies in its resistance to radiotherapy, chemotherapy, and immunotherapy [4], intra- and intertumor heterogeneity, and the heterotypic characteristics of pleomorphic RCC histology [5, 6]. …”

“…The nine tissue markers selected relate to either the hypoxia inducible factor (HIF-1) pathway, or the phosphatidylinositol 3-kinase pathway. The HIF-1 pathway, consisting of von Hippel Lindau, HIF-1, and vascular epithelial growth factor, and the phosphatidylinositol 3-kinase pathway, which includes protein kinase B and mammalian target of rapamycin (PI3K/Akt/mTOR), are two important molecular pathways responsible for oncogenesis, disease progression, metastasis, and neovascularization in RCC [4, 6, 8]…”

DNA Methylation Biomarkers Predict Progression-Free and Overall Survival of Metastatic Renal Cell Cancer (mRCC) Treated with Antiangiogenic Therapies

“…Due to different available compounds and a growing number of new agents affecting molecularly targeted structures, such as vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) signaling [4] an optimal sequence of targeted therapies might exist for patients, potentially increasing survival with mRCC treatment. Although prognostic models, such as the MSKCC (Memorial Sloan Kettering Cancer Center) and Heng scoring systems, have been reported to be independent predictors of clinical outcome, [5], [6] discrimination between outcomes is still limited.…”

Tivozanib: current status and future directions in the treatment of solid tumors

“…These so-called VEGF-tyrosine kinase inhibitors (VEGF-TKIs) have found wide application, ranging from gastrointestinal stromal tumor (GIST) to medullary thyroid cancer to HCC 16-18 . Clear cell mRCC is a disease particularly susceptible to this mode of angiogenesis inhibition, likely due to aberrations in the von Hippel Lindau ( VHL ) gene that prevent degradation of hypoxia inducible factor (HIF; a VEGF transcription factor) 19-20 . A total of four VEGF-TKIs have been approved for the treatment of mRCC on the basis of positive phase III studies: (1) sorafenib, (2) sunitinib, (3) pazopanib, and (4) axitinib 21-24 .…”