The multiple facets of drug resistance: one history, different approaches

Abstract

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.

Enrichment and characterization of cancer stem cells from a human non-small cell lung cancer cell line

“…Many tumors develop drug resistance during treatment. The reason is that CSCs can survive even in the presence of cytotoxic drugs (15). Since the activities of ABC transporters on the surface of CSCs are higher than that of non-CSCs, CSCs can discharge drugs leading to tumor regene sis (16).…”

Alkaloids from <i>Stephania venosa</i> as Chemo-Sensitizers in SKOV3 Ovarian Cancer Cells <i>via</i> Akt/NF-κB Signaling

“…and immune modulation (chemokines and interleukins) may contribute to the progression and development of tumor drug resistance. 1,2) To understand the underlying mechanisms of the chemo-sensitizing action on cisplatin sensitivity by aporphine in SKOV3, we checked the anti-apoptotic and survival proteins expression by Western blotting. Our results exhibited that cisplatin enhanced the expression of Bcl-xL, cIAP-2, survivin and IL-6, whereas this Previous studies have proposed that one of the causes of cancer drug resistance is the overexpression of Akt and its upstream mediator PI3K.…”

“…Cellular resistance to platinum can arise from various mechanisms related to decreased drug influx, increased DNA adduct repair, detoxification of platinum by intracellular thiols such as glutathione, alterations in intracellular signaling pathways and an increased efflux of drugs. 1,2) Exposure to cisplatin induces several cellular responses with consequent changes in growth regulation. Recent data suggest that the mitogen activated protein (MAP) kinase pathway, 3) the signal transducer and activator of transcription (STAT) pathway 4) and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway 5) get activated in response to cisplatin.…”

<b>Estudo da expressão imunoistoquímica de marcadores de resistência a múltiplas drogas em cães com linfoma cutâneo</b>

“…Um dos mecanismos subjacentes da resistência a múltiplas drogas (RMD) é o efluxo ativo de drogas por proteínas transportadoras da superfamília ATP-Binding Cassette (ABC), ligadas à membrana celular (LUQMANI, 2008;KUNJACHAN et al, 2013;NIERO et al, 2014;WONG et al, 2014;CHEN, 2017 Os transportadores da família ABC são encontrados em todos os organismos, mas a glicoproteína-P humana ABC (Pgp/ABCB1), a proteína associada a resistência a múltiplas drogas-1 (MRP1/ABCC1) e a proteína de resistência ao câncer de mama (BCRP/ABCG2) estão entre os mais estudados devido ao seu papel no desenvolvimento de RMD no câncer (MEALEY et al, 2003SCHINKEL;JONKER, 2003;LESLIE;COLE, 2005;LUQMANI, 2008;MEALEY, 2012;KUNJACHAN et al, 2013;NIERO et al, 2014;WONG et al, 2014;ZANDVLIET;SCHRICKX, 2014 A expressão da Pgp já foi relatada em muitos tumores caninos (GINN, 1996;HIFUMI et al 2010;LEE, 2007, MIYOSHI et al, 2002.…”

“…Outros mecanismos podem ser utilizados como o metabolismo enzimático do fármaco, a alteração do local alvo para prevenir a ligação ao fármaco, alteração da via metabólica e o aumento do reparo dos danos causados pelo fármaco (LUQMANI, 2008;NIERO et al, 2014;WONG et al, 2014;KAMBAYASHI et al, 2015;TOMASZOWSKI;SCHIRRMACHER;KAINA, 2015).…”