he antimalarial drug chloroquine (CQ) is presently being studied as a promising antitumor agent for a number of late-stage malignancies. Though its antitumor effect is due in part to its blockage of autophagy in cancer cells (1, 2), a recent report in Cancer Cell by Maes et al. demonstrated that CQ can also undermine cancers through an autophagy-independent mechanism. The authors showed that CQ activated Notch1 signaling in endothelial cells and enhanced tumor vessel normalization (3). This increased vascular integrity and perfusion may compromise cancer cell survival and behavior by not only facilitating the delivery and efficacy of cytotoxic therapies, but also by lessening metastatic potential through reduction of tumor hypoxia. The researchers further suggest that this improved vascular access to tumor masses may create new opportunities for immunotherapeutic intervention.