Book ChapterDOI
Mechanisms of multidrug resistance in cancer.
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TLDR
Identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict theDevelopment of resistance and lead to treatments designed to circumvent it.Abstract:
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis on ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram.read more
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Journal ArticleDOI
Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay
Daniel Martinez Molina,Rozbeh Jafari,Marina Ignatushchenko,Takahiro Seki,E. Andreas Larsson,Chen Dan,Lekshmy Sreekumar,Yihai Cao,Yihai Cao,Pär Nordlund,Pär Nordlund +10 more
TL;DR: This cellular thermal shift assay (CETSA) is based on the biophysical principle of ligand-induced thermal stabilization of target proteins and validated drug binding for a set of important clinical targets and monitored processes of drug transport and activation, off-target effects and drug resistance in cancer cell lines, as well as drug distribution in tissues.
Journal ArticleDOI
Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes
TL;DR: Decreased accumulation is one of the most common features resulting in cisplatin resistance, and seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisPlatin, and decreased fluid phase endocytosis.
Journal ArticleDOI
Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade.
Zhaolin Chen,Tianlu Shi,Lei Zhang,Pengli Zhu,Mingying Deng,Cheng Huang,Tingting Hu,Ling Jiang,Jun Li +8 more
TL;DR: Recent findings suggest that efflux pumps of the ABC transporter family are subject to epigenetic gene regulation, and this review summarizes recent findings of the role of ABC efflux transporters in MDR.
Journal ArticleDOI
The modulation of ABC transporter-mediated multidrug resistance in cancer: a review of the past decade.
TL;DR: The development of new compounds and the re-evaluation of compounds originally designed for other targets as transport inhibitors of ATP-dependent drug efflux pumps are summarized.
Journal ArticleDOI
The Clinical Relevance of Cancer Cell Lines
TL;DR: This work reviews the major events in the development of the in vitro models and the emergence of new technologies that have revealed important issues and limitations concerning human cancer cell lines as models and develops new in vitro preclinical models that would substantially increase the success rate ofnew in vitro-assessed cancer treatments.
References
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Journal Article
Cellular predictive factors for the drug response of lung cancer
Manfred Volm,Werner Rittgen +1 more
TL;DR: Analysis of cellular factors found that angiogenesis, as measured by the microvessel density and the angiogenic factors, is inversely correlated to the resistance of non-small cell lung cancer.
Journal ArticleDOI
Comparing the relationship of Taxol-based chemotherapy response with P-glycoprotein and lung resistance-related protein expression in non-small cell lung cancer.
TL;DR: Taxol-based chemotherapy response of patients with NSCLC was related to P-glycoprotein but not LPR expression, and the incidence difference of positive Pgp expressions between good and poor responses was significant, however, the difference of LRP expression was not.
Journal Article
Expression of the human major vault protein LRP in acute myeloid leukemia.
TL;DR: Data suggest that LRP gene overexpression may constitute a novel mechanism of multidrug resistance in patients with acute myeloid leukemia (AML) and ovarian carcinoma.
Journal ArticleDOI
Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy
Vassiliki Malamou-Mitsi,Helen Gogas,Urania Dafni,A Bourli,T Fillipidis,Maria Sotiropoulou,Dimitrios Vlachodimitropoulos,Stefanos Papadopoulos,Olympia Tzaida,Georgia Kafiri,Vasiliki Kyriakou,Sofia Markaki,Irini Papaspyrou,E Karagianni,Kitty Pavlakis,T. Toliou,Chrisoula D. Scopa,Pavlos Papakostas,Dimitris Bafaloukos,C. Christodoulou,George Fountzilas +20 more
TL;DR: Multivariate analysis revealed that, positive p53 expression, higher number of positive nodes and worse tumor grade were related to significantly poorer OS and DFS, and no predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident.
Journal Article
Expression of the Lung Resistance Protein Predicts Poor Outcome in Patients with Multiple Myeloma
Martin Filipits,Johannes Drach,Gudrun Pohl,Judith Schuster,Thomas Stranzl,Jutta Ackermann,Robert Königsberg,Hannes Kaufmann,Heinz Gisslinger,Heinz Huber,Heinz Ludwig,Robert Pirker +11 more
TL;DR: Data show that LRP expression is an important marker for clinical drug resistance and predicts a poor outcome in multiple myeloma and Kaplan-Meier analysis revealed that patients with L RP expression had a shorter overall survival than those without LRPexpression.