Perspectives in drug development for metastatic renal cell cancer

Abstract

Patients with renal cell carcinoma (RCC) exhibit a spectrum of clinical outcomes, with some patients following an indolent clinical course and others displaying rapidly advancing disease. As evidence points to RCC being largely refractory to traditional chemotherapy and radiotherapy strategies, immunotherapeutic approaches played a dominant role in the management of metastatic RCC for a quarter of a century. Management of this challenging tumor has been revolutionized by the incorporation of molecularly targeted therapies such as inhibitors of pathways involving tyrosine kinase signaling and the mammalian target of rapamycin (mTOR). The improvements in disease stabilization and survival seen with these agents has meant that molecularly targeted therapy now forms the foundation for treating RCC and has resulted in a multitude of studies investigating similar compounds for efficacy in RCC. Despite this, the rationale for using immunomodulatory regimens remains strong and its ongoing place in this era of targeted treatments continues to pose interesting clinical questions. The challenge of maintaining durable responses from our current therapies persists and this review highlights the plethora of options now available in RCC treatment and the directions in which modern management are heading.

Expression and significance of histone H3K27 demethylases in renal cell carcinoma

“…The two most common types of kidney cancer are renal cell carcinoma (RCC) and urothelial cell carcinoma. RCC is the most common kidney cancer in adults, and is generally resistant to chemotherapy and radiation therapy [4,5]. Radical or partial nephrectomy of the tumor at a localized stage remains the mainstay of curative therapy [6].…”

Chemokine and Chemokine Receptor Expression in Kidney Tumors: Molecular Profiling of Histological Subtypes and Association With Metastasis

“…Renal cell carcinoma (RCC) comprises of a spectrum of tumors, ranging from tumors with indolent clinical course to highly metastatic 1 . Histologically, clear cell RCC (ccRCC) comprises of > 70–80% of all RCC cases.…”

“…Thirty percent of all RCC patients present with disease that is too advanced for curative surgical resection. Furthermore, 30% of patients with local disease relapse after surgery 1–4 . Molecular characterization can lead to identification of markers that distinguish between indolent versus malignant RCC tumor types, accurately predict metastatic potential and aid in designing targeted therapies 5–7 .…”

Dimethoxycurcumin, a Structural Analogue of Curcumin, Induces Apoptosis in Human Renal Carcinoma Caki Cells Through the Production of Reactive Oxygen Species, the Release of Cytochrome c, and the Activation of Caspase-3

“…Renal carcinoma remains one of the most drug-resistant malignancies in humans and is a frequent cause of cancer mortality [18,19]. Interestingly, two studies have demonstrated that Cur can induce apoptosis in human renal carcinoma Caki cells [20,21].…”