title: Deconstructing breast cancer cell biology and the mechanisms of multidrug resistance.
abstract: Cancer complexity constantly challenges the way that clinicians manage breast cancer therapy. Tumor heterogeneity and intratumoral stroma characteristics allow cells with different phenotypes and deregulated apoptotic, proliferative and migration abilities to co-exist contributing to a disappointing therapeutic response. While new approaches are being associated with conventional chemotherapy, such as hormonal therapy or target monoclonal antibodies, recurrence and metastasization are still observed. Membrane transporters are the cell's first line of contact with anticancer drugs having a major role in multidrug resistance events. This structural-based activity enables the cell to be drug-resistant by decreasing drug intracellular concentration through an efflux-transport mechanism, mainly associated with overexpression of ATP-binding cassette (ABC) proteins. This review focuses on some of the important structural and biological properties of the malignant cell and tumor microenvironment, addressing the role of the membrane ABC transporters in therapeutic outcomes, and highlighting related molecular pathways that may represent meaningful target therapies.
authors: Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal; Department of Galenic Pharmacy and Pharmaceutical Technology, Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal. Electronic address: mvideira@ff.ul.pt.
authors: Mafalda
authors: M
authors: Videira
authors: Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
authors: Rita Leones
authors: RL
authors: Reis
authors: Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
authors: Maria Alexandra
authors: MA
authors: Brito
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D055354:Exosomes; D005260:Female; D006801:Humans; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1
keywords: Cancer biology; Chemoresistance; Efflux transporters; Epithelial-mesenchymal transition; Multidrug resistance proteins; Tumor microenvironment