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Chloroquine enjoys a renaissance as an antineoplastic therapy

Virginia Espina, Lance A Liotta

Chloroquine (CQ) and hydroxychloroquine (HCQ), oral lysosomotropic agents with well-studied toxicity profiles, and antimalarial and antirheumatic activity, have been repurposed as antineoplastic agents based on preclinical data showing efficacy in preinvasive cancer, cancer stem cells and metastatic cancer. Phase I/II clinical trials are providing safety and efficacy data regarding CQ or HCQ monotherapy or combination therapy with molecularly targeted inhibitors in patients diagnosed with glioblastoma multiforme, breast ductal carcinoma in situ, non-small-cell lung cancer, hepatocellular, pancreatic, or renal cancer, multiple myeloma, or chronic lymphocytic leukemia. Disruption of autophagy-mediated cell survival is a major therapeutic rationale for using CQ and HCQ. CQ and HCQ are the first agents that rationally target cytoprotective autophagy in cancer. Short-term treatment of preinvasive breast cancer with CQ introduces the concept of preventing invasive cancer by killing preinvasive lesions.