Chloroquine and hydroxychloroquine for cancer therapy.
Macroautophagy (herein referred to as autophagy) is a highly conserved mechanism for the lysosomal degradation of cytoplasmic components. Autophagy is critical for the maintenance of intracellular homeostasis, both in baseline conditions and in the context of adaptive responses to stress. In line with this notion, defects in the autophagic machinery have been etiologically associated with various human disorders including infectious, inflammatory and neoplastic conditions. Once tumors are established, however, autophagy sustains the survival of malignant cells, hence representing an appealing target for the design of novel anticancer regimens. Accordingly, inhibitors of autophagy including chloroquine and hydroxychloroquine have been shown to mediate substantial antineoplastic effects in preclinical models, especially when combined with chemo- or radiotherapeutic interventions. The pharmacological profile of chloroquine and hydroxychloroquine, however, appear to involve mechanisms other than autophagy inhibition. Here, we discuss the dual role of autophagy in oncogenesis and tumor progression, and summarize the results or design of clinical studies recently completed or initiated to evaluate the therapeutic activity of chloroquine derivatives in cancer patients.
Regina Elena National Cancer Institute; Rome, Italy.
Gwenola
G
Manic
Université Paris-Sud/Paris XI; Le Kremlin-Bicêtre, France; INSERM, UMRS1138; Villejuif, France; Equipe 11 labelisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers; Paris, France.
Florine
F
Obrist
INSERM, UMRS1138; Villejuif, France; Equipe 11 labelisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers; Paris, France; Metabolomics and Cell Biology Platforms; Gustave Roussy Cancer Campus; Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP; Paris, France.
Guido
G
Kroemer
Regina Elena National Cancer Institute; Rome, Italy.
Ilio
I
Vitale
Regina Elena National Cancer Institute; Rome, Italy; Equipe 11 labelisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers; Paris, France; Université Paris Descartes/Paris V; Sorbonne Paris Cité; Paris, France.
Lorenzo
L
Galluzzi
autophagosomes; bafilomycin A1; beclin 1; lysosomes; mTOR; proteasome