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Cancer drug resistance: an evolving paradigm

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TLDR
There are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.
Abstract
Resistance to chemotherapy and molecularly targeted therapies is a major problem facing current cancer research. The mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to therapies that are designed to be selective for specific molecular targets share many features, such as alterations in the drug target, activation of prosurvival pathways and ineffective induction of cell death. With the increasing arsenal of anticancer agents, improving preclinical models and the advent of powerful high-throughput screening techniques, there are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.

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Journal ArticleDOI

Drug Resistance in Cancer: An Overview

TL;DR: The current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance are outlined.
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Cancer stem cells revisited

TL;DR: New developments in the cancer stem cell field are discussed in relationship to changing insights into how normal stem cells maintain healthy tissues and the first successes of therapies based on the CSC concept are emerging.
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EMT, CSCs, and drug resistance: the mechanistic link and clinical implications

TL;DR: In this paper, the authors discuss the link between the epithelial-to-mesenchymal transition (EMT) and the cancer stem cell (CSC) phenotype and discuss how this knowledge can contribute to improvements in clinical practice.
Journal Article

Novel mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia.

TL;DR: It is reported that PTEN activation contributes to trastuzumab's antitumor activity and PTEN deficiency is a powerful predictor for trastzumab resistance, suggesting that PI3K-targeting therapies could overcome this resistance.
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Metastatic colonization by circulating tumour cells

TL;DR: An improved understanding of the mechanistic determinants of such colonization is needed to better prevent and treat metastatic cancer.
References
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Journal ArticleDOI

The hallmarks of cancer.

TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

TL;DR: BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.
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Multidrug resistance in cancer: role of ATP–dependent transporters

TL;DR: The ability to predict and circumvent drug resistance is likely to improve chemotherapy, and it has become apparent that resistance exists against every effective drug, even the authors' newest agents.
Journal ArticleDOI

New perspectives in cell adhesion : RGD and integrins

TL;DR: Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.
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