The multiple facets of drug resistance: one history, different approaches.
Some cancers like melanoma and pancreatic and ovarian cancers, for example, commonly display resistance to chemotherapy, and this is the major obstacle to a better prognosis of patients. Frequently, literature presents studies in monolayer cell cultures, 3D cell cultures or in vivo studies, but rarely the same work compares results of drug resistance in different models. Several of these works are presented in this review and show that usually cells in 3D culture are more resistant to drugs than monolayer cultured cells due to different mechanisms. Searching for new strategies to sensitize different tumors to chemotherapy, many methods have been studied to understand the mechanisms whereby cancer cells acquire drug resistance. These methods have been strongly advanced along the years and therapies using different drugs have been increasingly proposed to induce cell death in resistant cells of different cancers. Recently, cancer stem cells (CSCs) have been extensively studied because they would be the only cells capable of sustaining tumorigenesis. It is believed that the resistance of CSCs to currently used chemotherapeutics is a major contributing factor in cancer recurrence and later metastasis development. This review aims to appraise the experimental progress in the study of acquired drug resistance of cancer cells in different models as well as to understand the role of CSCs as the major contributing factor in cancer recurrence and metastasis development, describing how CSCs can be identified and isolated.
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av, Prof, Lineu Prestes, 1524, Cidade Universitária, 05508-000 São Paulo, SP, Brazil. eloniero@yahoo.com.
Evandro Luís
EL
Niero
Bianca
B
Rocha-Sales
Camila
C
Lauand
Beatriz Araujo
BA
Cortez
Marcelo Medina
MM
de Souza
Paula
P
Rezende-Teixeira
Marcel Shiniti
MS
Urabayashi
Adam Arai
AA
Martens
Jorge Henrique
JH
Neves
Gláucia Maria
GM
Machado-Santelli
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006360:Heat-Shock Proteins