Considering that human cells sensitively respond to spike and/or its S1 subunit to elicit ACE2 cell signaling and ACE2 exerts multiple anti-tumoral and anti-invasive effects, including the inhibition of cancer angiogenesis and metastasis, the prolonged (or even transient) spike-mediated ACE2 downregulation (or loss) could per se promote tumor progression [83-86]. The gene discussed is ACE2; the disease is cancer.