Book ChapterDOI
Mechanisms of multidrug resistance in cancer.
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Pharmacogenomics of soft tissue sarcomas: New horizons to understand efficacy and toxicity.
Gambale Elisabetta,Boddi Anna,Pasqui Adriano,Campanacci Domenico Andrea,Scoccianti Guido,Palchetti Ilaria,Bernini Andrea,Antonuzzo Lorenzo,Pillozzi Serena +8 more
TL;DR: In this paper , the detection of pharmacogenomics (PGx) biomarkers that might predict drug response and toxicity can be useful to explain the genetic basis for the differences in treatment efficacy and toxicity among STS patients.
Patent
Use of nobiletin in cancer treatment
TL;DR: In this paper, a pharmaceutical composition of treating multidrug resistance cancer, comprising a citrus methoxyflavone and a chemotherapeutic drug, in which the citrus methoxide is nobiletin, was presented.
Journal ArticleDOI
Cell cycle associated miRNAs as target and therapeutics in lung cancer treatment
Atqiya Fariha,Ithmam Hami,Mahafujul Islam Quadery Tonmoy,Shahana Akter,Hasan Al Reza,Newaz Mohammed Bahadur,Md. Mizanur Rahaman,Md. Shahadat Hossain +7 more
TL;DR: In this article , the role of microRNA (miRNA) driven cell cycle regulation in lung cancer progression is discussed. But, the authors focus on early diagnosis and treatment strategies to prevent lung cancer.
Journal ArticleDOI
Overview of mitoxantrone-a potential candidate for treatment of breast cancer
TL;DR: Mitoxantrone is an ABC-transporter in breast cancer, also designated to be associated with “Breast cancer resistance protein” (BCRP) and it is also a cell cycle non-specific anti-cancer drug and P-glycoprotein substrate.
Book ChapterDOI
Small Molecule Chemosensitizing Agents: Polo-Like Kinase 1 (Plk1), BRAF and Janus Kinase (JAK) Inhibitors
TL;DR: This chapter provides a summary of some of the major findings comparing ABC drug transporter interactions with inhibitors of polo-like kinase 1, BRAF, and Janus kinase.
References
More filters
Journal ArticleDOI
ONCOMINE: A Cancer Microarray Database and Integrated Data-Mining Platform
Daniel R. Rhodes,Jianjun Yu,K. Shanker,Nandan P. Deshpande,Radhika Varambally,Debashis Ghosh,Terrence R. Barrette,Akhilesh Pandey,Arul M. Chinnaiyan +8 more
TL;DR: ONCOMINE is presented, a cancer microarray database and web-based data-mining platform aimed at facilitating discovery from genome-wide expression analyses and novel biomarkers and therapeutic targets are discovered.
Journal ArticleDOI
A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants.
TL;DR: Observations on the molecular basis of pleiotropic drug resistance are interpreted in terms of a model wherein certain surface glycoproteins control drug permeation by modulating the properties of hydrophobic membrane regions.
Journal ArticleDOI
Targeting multidrug resistance in cancer
Gergely Szakács,Jill K. Paterson,Joseph A. Ludwig,Catherine Booth-Genthe,Michael M. Gottesman +4 more
TL;DR: Various approaches to combating multidrug-resistant cancer are described, including the development of drugs that engage, evade or exploit efflux by ABC transporters.
Journal ArticleDOI
Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line
Susan P.C. Cole,Gabu Bhardwaj,James H. Gerlach,J. E. Mackie,Caroline E. Grant,Kurt C. Almquist,Alistair J. Stewart,Ebba U. Kurz,A. M. V. Duncan,Roger G. Deeley +9 more
TL;DR: Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression, and the mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.
Journal ArticleDOI
A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity
Chava Kimchi-Sarfaty,Jung Mi Oh,In-Wha Kim,Zuben E. Sauna,Anna Maria Calcagno,Suresh V. Ambudkar,Michael M. Gottesman +6 more
TL;DR: It is hypothesized that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.