Alternatively, upon inactivation of tumor suppressors, drugs can restore tumor suppressor function (e.g. belzutifan inhibiting HIF-2α in case of missing ubiquitylation due to PGVs in VHL), or indirectly target downstream signaling (e.g. mTOR inhibition due to PGVs in TSC1/2 or MEK inhibition due to PGVs in NF1). This evidence concerns the gene EPAS1 and neoplasm.