A brief note on Cancers of the kidney and renal pelvis


A brief note on Cancers of the kidney and renal pelvis

Cancers of the kidney and renal pelvis represent a constellation of types but the most common are renal cell carcinoma (RCC) in the kidney and transitional cell carcinoma in the renal pelvis and ureter. Identification in 1993 of the von Hippel-Lindau (VHL) gene on chromosome 3p25-26 began a trend to greater understanding of the molecular mechanisms of renal tumors.

An inherited mutation of one gene copy defines the disease, and somatic mutation or epigenetic silencing of the remaining allele leads to the disease phenotype. The VHL mutation results in loss of the E3 ubiquitin ligase complex degradation of hypoxia-inducible factor-α (HIF-α). This permits build-up of HIF-α with increased downstream signalling that promotes cell survival and angiogenesis.

Invasive tumors demonstrating loss of VHL consistently demonstrate additional genetic changes, which appear also to be essential for tumor progression. These altered events now provide targets for new therapies that have improved the progression-free and overall survival of patients with this disease. Although systemic therapies exist, metastatic disease is still virtually incurable.

The etiology of kidney cancer is imperfectly understood. The cellular and molecular basis must be elucidated so that effective treatments may be designed. Infection and inflammation appear to be significant in prostate cancer and may be in kidney cancer as well. Environmental factors clearly play a role. Some are similar to bladder cancer associated factors (tobacco, occupational exposure), while others are more specific to carcinogenesis of the upper urinary tract, including phenacetin, Balkan endemic nephropathy, Chinese herb nephropathy, Blackfoot disease (chronic arsenic poisoning) and possibly aristolochic acid.

Early detection is critical, and the ease of obtaining urine dictates the development of cell or protein based screening tools for which genomic, proteomic or metabolomic markers must be sought, and detection methods developed and validated.

Journal of Nephrology and Urology is an Open Access peer-reviewed publication that discusses current research and advancements in diagnosis and management of kidney disorders as well as related epidemiology, pathophysiology and molecular genetics

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