Abstract
In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) has led to the development of biologically-driven targeted therapies. Hypoxia-inducible factors (HIFs), angiogenic growth factors, von Hippel–Lindau (VHL) gene mutations, and oncogenic microRNAs (miRNAs) play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of vascular endothelial growth factor (VEGF) inhibitors, Mechanistic target of rapamycin (mTOR) inhibitors, and immunotherapeutic agents, which have significantly improved the outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC) inhibitors, selenium, and agents like PT2385 and PT2977 are being explored in various clinical trials as potential HIF inhibitors, to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in clear cell RCC (ccRCC) tumors.
Highlights
Clear cell renal cell carcinoma is the most common malignancy in the kidney
Renal cell carcinoma (RCC) is categorized into three major histological subtypes: Clear cell renal cell carcinoma (ccRCC), comprising 70% of cases; papillary and chromophobe RCC, which together comprise 25% of cases; and tumors of the medullary
In a phase III non-inferiority trial, pazopanib was compared to sunitinib in patients with advanced renal cell carcinoma
Summary
Clear cell renal cell carcinoma (ccRCC) is the most common malignancy in the kidney. Over 65,000 new kidney cancer cases and 14,000 deaths were estimated in the United States in 2018 [1]. Renal cell carcinoma (RCC) is the most lethal genitourinary cancer, given that its disease course is largely asymptomatic and incidentally found in more than half of new cases [2,3]. Established modifiable risk factors for RCC include obesity, smoking, and hypertension [4]. Other studies link alcohol use, type 2 diabetes, and occupational or environmental exposures to increased risk of RCC [5]. This is mediated via transcAridpatpiotantiofnacttoorashcyaplloexdic heynvpioroxniam-ienndt uisciablkeeyfaactttorirbsut(eHoIfFsc)a.ncTerheceslels.faTchtoisrsis amreedhiaetteedrovdiaimers with tarannsαc-rsiputbiounnfiatc(toHrsIFc1aαlle,dHhIyFp2oαx,iao‐irndHuIcFib3lαe )faactnodrs a(HβIF-s)u. FigurFeig1u. rIenh1i.bIintohribsiotofrtsheofhtyhpeohxyiap-oinxidau‐icnidbulecifbalcetofarc(tHorIF(H) pIFa)thpwatahywcauyrrceunrtrleyntblyeinbgeinegvaeluvaaltueadteidn cinlinical trials.clVinHicLal:tvrioanls.HViHpLp:evl–oLniHndipapue;l–HLIinFd: hauy;pHoIxFi:ah-iynpdouxicai‐binledufaccibtolerfsa;cHtoDrsA; HCD: hAiCst:ohnisetodneeadceeatyceltayslea;seV; EGF: vascuVlaErGeFn: dvoastchuellairalengdroowthtehliaflagctrorw; tLhDfaHct:olra;cLtDatHe:dlaechtyatderdoegheyndarsoeg;eGnaLsUe;TG1L: UglTu1c: ogsluectorsaentsrpanosrpteorrt1e.r
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