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Review
. 2013 Aug;40(4):511-20.
doi: 10.1053/j.seminoncol.2013.05.009.

Non-clear cell renal cancer: disease-based management and opportunities for targeted therapeutic approaches

W Marston Linehan  1 , Ramaprasad Srinivasan, Jorge A Garcia
Affiliations
Review

Non-clear cell renal cancer: disease-based management and opportunities for targeted therapeutic approaches

W Marston Linehan et al. Semin Oncol. 2013 Aug.

Abstract

A better understanding of the biology of renal cell carcinoma (RCC) has significantly changed the treatment paradigm of the disease. Several novel vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have been approved recently by the US Food and Drug Administration. Unfortunately, the vast majority of clinical trials conducted today have been aimed to include patients with clear cell RCC, which remains the most common histologic subtype of the disease. Non-clear cell RCC represents approximately 20%-25% of all RCC patients. Non-clear cell RCC is made up of multiple histologic subtypes, each with a different molecular printing profile. Although VEGF and TORC inhibitors are commonly used in the management of this cohort of patients, non-clear cell histologies do not appear to be related to the von Hippel-Lindau gene (VHL). As such, the clinical efficacy of the existing agents is quite limited. There is a need to develop more rational therapeutic approaches that specifically target the biology of each of the different subtypes of non-clear cell RCC. In this review, we discuss molecular and clinical characteristics of each of the non-clear cell RCC subtypes and describe ongoing efforts to develop novel agents for this subset of patients.

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Figures

Figure 1
Figure 1. Non-Clear Cell Kidney Cancer
Non-clear cell kidney cancer is not a single disease, it is made up of a number of different types of cancer, each with a different histology, a different clinical course, responding differently to therapy and caused by a different gene. Adapted from Linehan, 2012 (88)
Figure 2
Figure 2. Non-Clear Cell Kidney Cancer Pathways
Non-clear cell kidney cancer is a metabolic disease. The genes that are associated with non-clear cell kidney cancer, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TFE3, TFEB, MITF, TSC1, TSC2, and PTEN are all associated with abnormalities of the cell’s ability to sense oxygen, iron, nutrients or energy. Adapted from Linehan, 2012 (88)
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