hydroxychloroquine + sorafenib

Hydroxychloroquine + sorafenib is an oral small‑molecule combination regimen under clinical investigation primarily for advanced or metastatic hepatocellular carcinoma and other refractory solid tumors. Sorafenib is a multikinase inhibitor targeting RAF/MEK/ERK signaling and pro‑angiogenic receptors such as VEGFR and PDGFR to inhibit tumor cell proliferation and angiogenesis, but it induces cytoprotective autophagy that contributes to acquired resistance. Hydroxychloroquine is a lysosomotropic agent that blocks autophagosome–lysosome fusion, thereby inhibiting autophagic flux; in preclinical HCC models, adding hydroxychloroquine to sorafenib synergistically re-sensitizes sorafenib‑resistant cells by modulating TLR9-driven pathways, reducing oxidative stress–related DNA damage, and enhancing apoptosis, and multiple phase II trials are testing whether this autophagy inhibition strategy improves clinical outcomes compared with sorafenib alone in solid tumors and liver cancer.

Brand names

PlaquenilNexavar

Other names

hydroxychloroquine + sorafenibHCQ + sorafeniboral hydroxychloroquine plus oral sorafenib