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Le et al. J Transl Genet Genom 2018;2:17. I https://doi.org/10.20517/jtgg.2018.28 Page 3 of 9

Figure 1. Chromosome 3p tumor suppressor genes of kidney cancer and their major functions

Figure 2. Diagram depicts the time line of renal cell carcinoma therapeutic development with 13 approved drugs representing 7 different
mechanisms

[20]
been associated with increased risk of developing kidney cancer in the general population . Therefore in
human ccRCC, disease progression and mortality have been associated with HIF-2α overexpression rather
[21]
than HIF-1α, which is often silenced by gene deletion . Altogether, HIF-1 probably plays an essential role in
tumor initiation, whereas HIF-2 is needed for tumor progression.

Identification of HIFs as renal oncogenes and their downstream targets have led to development of many
currently approved and investigational therapies for systemic treatment of advanced or locally unresectable
ccRCC. Given the dependence of ccRCC tumors on angiogenesis for growth, inhibitors of VEGF and VEGF
receptor tyrosine kinases, such as bevacizumab, sorafenib sunitinib, pazopanib, and axitinib, cabozantinib,
[22]
and lenvatinib have been developed and are widely used as first or second-line therapies [Figure 2] . Small