title: Drugs acting on homeostasis: challenging cancer cell adaptation.
abstract: Cancer treatment aims to exploit properties that define malignant cells. In recent years, it has become apparent that malignant cells often survive cancer treatment and ensuing cell stress by switching on auxiliary turnover pathways, changing cellular metabolism and, concomitantly, the gene expression profile. The changed profile impacts the material exchange of cancer cells with affected tissues. Herein, we show that pathways of proteostasis and energy generation regulate common transcription factors. Namely, when one pathway of intracellular turnover is blocked, it triggers alternative turnover mechanisms, which induce transcription factor proteins that control expression of cytokines and regulators of apoptosis, cell division, differentiation, metabolism, and response to hormones. We focus on several alternative turnover mechanisms that can be blocked by drugs already used in clinical practice for the treatment of other non-cancer related diseases. We also discuss paradigms on the challenges posed by cancer cell adaptation mechanisms.
authors.affiliation: a 1 University of Athens, Horemio Research Institute, First Department of Pediatrics, Thivon & Levadeias, Goudi, Athens, 11527, Greece.|b 2 University of Athens, Pediatric Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sofia" Children's Hospital, Thivon & Levadeias, 11527 Goudi, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Moschovi
authors.affiliation: a 1 University of Athens, Horemio Research Institute, First Department of Pediatrics, Thivon & Levadeias, Goudi, Athens, 11527, Greece.
authors.forename: Elena
authors.initials: E
authors.lastname: Critselis
authors.affiliation: c 3 Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago Ave, Chicago, IL 60611, USA.
authors.forename: Osman
authors.initials: O
authors.lastname: Cen
authors.affiliation: a 1 University of Athens, Horemio Research Institute, First Department of Pediatrics, Thivon & Levadeias, Goudi, Athens, 11527, Greece.|b 2 University of Athens, Pediatric Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sofia" Children's Hospital, Thivon & Levadeias, 11527 Goudi, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Adamaki
authors.affiliation: a 1 University of Athens, Horemio Research Institute, First Department of Pediatrics, Thivon & Levadeias, Goudi, Athens, 11527, Greece.
authors.forename: George I
authors.initials: GI
authors.lastname: Lambrou
authors.affiliation: a 1 University of Athens, Horemio Research Institute, First Department of Pediatrics, Thivon & Levadeias, Goudi, Athens, 11527, Greece.
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.affiliation: a 1 University of Athens, Horemio Research Institute, First Department of Pediatrics, Thivon & Levadeias, Goudi, Athens, 11527, Greece.
authors.forename: Spiros
authors.initials: S
authors.lastname: Vlahopoulos
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D014157:Transcription Factors
keywords: cell stress; gene promoter; homeostasis; immune system; metabolism; signal transduction