Abstract
Renal cell carcinoma (RCC) is a highly vascularized tumor type, which is often associated with inactivated mutations in the von Hippel-Lindau gene that drives proangiogenic signaling pathways. As such, new therapies for the treatment of RCC have largely been focused on blocking angiogenesis. Sunitinib, an antiangiogenic tyrosine kinase inhibitor, is the most frequently used first-line drug for the treatment of RCC. Although treatment with sunitinib improves patient outcome considerably, acquired resistance will emerge in all cases. The molecular mechanisms of resistance to sunitinib are poorly understood, but in the past decade, several of these have been proposed. Lysosomal sequestration of sunitinib was reported as a potential resistance mechanism to sunitinib. In this review, the underlying molecular mechanisms of lysosomal sunitinib sequestration and the potential strategies to overcome this resistance are discussed to be able to further improve the treatment of RCC.
Highlights
Kidney cancer is one of the fastest growing cancers worldwide
Renal cell carcinoma (RCC) is highly resistant to traditional cancer treatments, such as radiation therapy and chemotherapy [3]
A better biological understanding of RCC has resulted in a rational development of targeted therapies, such as antiangiogenic tyrosine kinase inhibitors (TKIs)
Summary
Kidney cancer is one of the fastest growing cancers worldwide. It is the ninth most common cancer type in men and the 14th most common cancer type in women, with approximately 214,000 and 124,000 patients, respectively. The most common renal RCC subtypes are clear cell (75%), papillary (15%), chromophobic (5%), and collecting duct carcinoma (2%) [2]. RCC is highly resistant to traditional cancer treatments, such as radiation therapy and chemotherapy [3]. A better biological understanding of RCC has resulted in a rational development of targeted therapies, such as antiangiogenic tyrosine kinase inhibitors (TKIs). TKIs, such as sunitinib, pazopanib, and axitinib, are approved by the Food and Journal of Kidney Cancer and VHL 2015; 2(4):195203. TKIs, such as sunitinib, pazopanib, and axitinib, are approved by the Food and Journal of Kidney Cancer and VHL 2015; 2(4):195-203. http://jkcvhl.com
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