title: Microenvironment and autophagy cross-talk: Implications in cancer therapy.
abstract: There are many ongoing clinical trials to validate tumour microenvironment or autophagic pathway components as targets for anticancer therapies. Different components of the tumour microenvironment play important roles in tumour cell responses, directly affecting malignant transformation, drug resistance and metastasis. Autophagy is also related to chemotherapy responses by inducing tumour cell death or survival. Thus, the autophagy pathway may act as oncosuppressor, in addition to protecting cells from chemotherapy. The cross-talk between the microenvironment and autophagy is very complex and poorly understood. In a recent study using a three-dimensional (3D) cell culture model, the well-documented chemotherapy-mediated activation of autophagy was impaired in breast cancer cells, suggesting a context-dependent outcome for autophagy modulators, under the control of the p53 protein. A deeper understanding of this microenvironment/autophagy interplay may provide important clues for identifying differences in the tumour cell signalling network from in vitro basic research studies to the actual clinical context. In this work, we summarize the role of the microenvironment and autophagy in physiological and tumourigenic conditions, their interactions, and the challenges related to the use of drugs that target these pathways in cancer treatment protocols, emphasizing the potential use of 3D cell culture models in preclinical studies.
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil. Electronic address: luciana.gomes@usp.br.
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Gomes
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil. Electronic address: avessoni@wustl.edu.
authors.forename: Alexandre T
authors.initials: AT
authors.lastname: Vessoni
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil. Electronic address: cfmmenck@usp.br.
authors.forename: Carlos F M
authors.initials: CFM
authors.lastname: Menck
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents
keywords: Autophagy; Cancer; Chemotherapy; Microenvironment