Molecular mechanisms, therapeutic targets, and clinically tested drugs in AIDS-KS paracrine viral oncogenesis.

<p>In KS spindle cells lytically infected with KSHV cells or latently infected spindle cells expressing early lytic genes, KSHV genes such vGPCR, K1, and ORF45 constitutively trigger signaling cascades, leading to mTOR and ROS activation, which induce transcription and translation of PDGF and VEGF. These secreted growth factors can act in a paracrine manner to activate the same signaling cascades in latently infected cells expressing VEGF and PDGF receptors to drive KS cell proliferation and angiogenesis. Rapamycin (RAPA), which inhibits mTOR, and Imatinib (IMA), which inhibits PDGFR, can interrupt this paracrine loop to target KSHV tumorigenesis. Both drugs have shown efficacy in AIDS-KS clinical trials.