MANAGEMENT THERAPY AND HORMONAL REGULATION IN RENAL CELL CARCINOMA: A REVIEW

Saurabh Bhardwaj, Vijay Pal Singh, Ritu Sanwal1*, Sanjay Singh, Waseem Khan1, Sumit Joshi

ABSTRACT

Renal cancer (RC) accounts for around 3% of all adult malignancies and is the twelfth most common cancer in the world, with 338,000 new cases diagnosed in 2012 and around 100,000 deaths annually. Cancers of the kidney are more common in men than in women, and over the last few decades, the incidence has been increasing in many parts of the world. About 59% of RC cases occur in more developed countries. The global incidence rates are highest in Europe, North America and Australia and lowest in Africa, India and China. The Czech Republic has the highest rate of RC in the world, followed by Lithuania and Slovakia. The incidence in the Czech Republic to 2012 was reported as 24.1 (men) and 10.5 (women) per 100,000 people per year. This accounts in the Czech Republic for around 2,000 partial or radical nephrectomies yearly. Renal cell carcinoma (RCC) accounts for 80-85% of kidney cancers. It is the most common kidney variety and the third most commonly diagnosed urogenital. The most frequent histological type of RCC is clear cell renal cell carcinoma (ccRCC), with a prevalence of 75% of all primary kidney cancers. Papillary and chromophobe RCC are two less common subtypes. The American Cancer Society estimates that ap-proximately 63,990 patients will be diagnosed with renal cancer in the United States in 2017. In addition, approximately 14,400 patients are projected to die in 2017 from renal cancer. Renal cancer is one of the 10 most common malignancies in men and women in the United States. In recent years, the incidence of this disease has been on the rise. Despite this, the death rates are declining, as a result of the evolving landscape of renal cancer treatment with the developments in targeted therapies. Epidemiological, clinical, biochemical and genetic research has revealed that renal cell cancer (RCC) etiology is hormone-related. It was shown that hormone receptors are abnormally expressed in RCC cells. Abnormal endocrine stimulation also plays a significant role in RCC pathophysiology. Cellular proliferation, migration, angiogenesis, and drug resistance in RCC is modulated by para- and autocrine hormonal stimulation. In particular, RCC overexpression of gonadotropin-releasing hormone and its receptor was reported. On the contrary, corticotropin releasing hormone was reported to inhibit RCC cell proliferation and regulate angiogenesis. Overexpression of luteinizing hormone also promotes RCC tumor angiogenesis. Estrogen receptor α overexpression increases the transcriptional factor activity of hypoxia inducible factor HIF-1α, but estrogen receptor β has a cancer suppressive role. Glucocorticoid receptors and androgen receptors are markers of indolent RCC and assigned tumor suppressive activity. Proopiomelanocortin is upregulated in VHL-mutation renal cell carcinoma via Nur77 transcription factor signaling. In RCC, follicle-stimulating hormone receptors promote angiogenesis and metastatic formation via VEGF release. Mineralocorticoid receptor overexpression promotes cell survival and increases RCC cell proliferation. Vitamin D receptor expression is downregulated or absent in RCC and differentiates subtypes of renal cell tumors. RAR-βpromotes tumorigenesis but retinoic acid receptor γ expression correlates negatively with the TNM stage at diagnosis. Finally, progesterone receptor expression is negatively correlated with the cancer stage. Molecular data analysis revealed the possibility of renal cancer cell proliferation induction via hormone activated pathways. Inhibition of hormonal signaling may thus play a putative role in supportive therapies against this cancer type. This review provides basic information about the renal carcinoma, diagnostic parameters, Classification and types of pathology, prevention and management including hormonal regulation process involved in renal cell cancer. It was also to examine the current evidence for management therapies in RCC, discuss ongoing clinical trials and suggest future directions in the search for an effective management therapy.

Keywords: Renal carcinoma, Diagnostic parameters, Classification, Types of Pathology, Prevention and Management, Hormonal Regulation Process.