title: Regulation of tumor cell dormancy by tissue microenvironments and autophagy.
abstract: The development of metastasis is the major cause of death in cancer patients. In certain instances, this occurs shortly after primary tumor detection and treatment, indicating these lesions were already expanding at the moment of diagnosis or initiated exponential growth shortly after. However, in many types of cancer, patients succumb to metastatic disease years and sometimes decades after being treated for a primary tumor. This has led to the notion that in these patients residual disease may remain in a dormant state. Tumor cell dormancy is a poorly understood phase of cancer progression and only recently have its underlying molecular mechanisms started to be revealed. Important questions that remain to be elucidated include not only which mechanisms prevent residual disease from proliferating but also which mechanisms critically maintain the long-term survival of these disseminated residual cells. Herein, we review recent evidence in support of genetic and epigenetic mechanisms driving dormancy. We also explore how therapy may cause the onset of dormancy in the surviving fraction of cells after treatment and how autophagy may be a mechanism that maintains the residual cells that are viable for prolonged periods.
authors.affiliation: Department of Medicine and Otolaryngology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Maria Soledad
authors.initials: MS
authors.lastname: Sosa
authors.forename: Paloma
authors.initials: P
authors.lastname: Bragado
authors.forename: Jayanta
authors.initials: J
authors.lastname: Debnath
authors.forename: Julio A
authors.initials: JA
authors.lastname: Aguirre-Ghiso
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001343:Autophagy; D059447:Cell Cycle Checkpoints; D015687:Cell Hypoxia; D002465:Cell Movement; D002470:Cell Survival; D059865:Endoplasmic Reticulum Stress; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins