For some therapeutics, starting at an initial high dose, then tapering to tolerability can be a strategy to drive response e.g. of the various anti-PD-1/L1 plus VEGFR inhibitor combinations in renal cell carcinoma, lenvatinib plus pembrolizumab involves a relatively high initial dose of the VEGFR inhibitor (20mg lenvatinib) and has the highest reported response rate, even if subsequent dose reduction are common and survival benefit is very similar to the other combination (22). Here, KDR is linked to hereditary clear cell renal cell carcinoma.