The role of inflammation in kidney cancer

Renal cell carcinoma (RCC) constitutes more than 90 % of primary kidney tumors with the development of metastatic disease in the lung, bone, liver, and brain. Clear-cell RCC (CCRCC) is the most common histologic form of sporadic kidney cancer where the majority of tumors have inactivation of the von...

Full description

Saved in:

Bibliographic Details
Published in:	Advances in experimental medicine and biology Vol. 816; p. 197
Main Authors:	de Vivar Chevez, Antonio Roma, Finke, James, Bukowski, Ronald
Format:	Journal Article
Language:	English
Published:	United States 01-01-2014
Subjects:	Animals Anti-Inflammatory Agents - therapeutic use Carcinoma, Renal Cell - etiology Carcinoma, Renal Cell - pathology Carcinoma, Renal Cell - therapy Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - immunology Humans Inflammation - complications Inflammation - drug therapy Inflammation - genetics Inflammation Mediators - physiology Kidney Neoplasms - etiology Kidney Neoplasms - pathology Kidney Neoplasms - therapy Signal Transduction - genetics Signal Transduction - immunology
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Renal cell carcinoma (RCC) constitutes more than 90 % of primary kidney tumors with the development of metastatic disease in the lung, bone, liver, and brain. Clear-cell RCC (CCRCC) is the most common histologic form of sporadic kidney cancer where the majority of tumors have inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene resulting in the accumulation of hypoxia-inducible factor (HIF) leading to dysregulation of cell growth and angiogenesis. Understanding of the genetic changes in RCC and the downstream events have led to the development of tyrosine kinase inhibitors (TKI) that target HIF-regulated proteins which currently represents front-line therapy for metastatic disease although resistance develops in most patients overtime. Despite the fact that RCC is an immunogenic tumor, there is mounting evidence that immune cells and inflammatory pathways can enhance tumor growth and immune escape. However, recent studies are beginning to uncover the mechanisms of immune escape in RCC, and the role inflammatory immune cells and cytokines play is this process. These new findings have led to renewed interest in the use of immunotherapy for the treatment of this disease that includes strategies to regulate inflammatory responses. Here, we will discuss the different inflammatory signaling pathways (e.g., VHL, hypoxia, TNF-α, STAT, and TGF-β) and the downstream transcription factors, cytokines, and chemokines involved in tumor development, and disease progression. This will include assessment of the role inflammatory molecules (e.g., pVHL, TGFb, IL6, select chemokines/chemokine receptors) play in promoting cell transformation, survival, proliferation of tumor cells, and metastasis derived from in vitro and in vivo studies. Included is a section on how select inflammatory cells (TAM, MDSC, and neutrophils) promote tumor evasion of immune cells. We also provide examples of molecules/cells that correlate negatively (CXCL12, CXCR4, and MMP, neutrophils, and MDSC) and positively (TH1 cells, IP-10, and MIG) with tumor progression and survival. Finally, there is a discussion of different inhibitors of inflammation that may be useful in the treatment of RCC.
ISSN:	0065-2598
DOI:	10.1007/978-3-0348-0837-8_9