Resistance To Taxanes

Greenberger, Lee M.; Sampath, Deepak

doi:10.1007/978-1-59745-035-5_18

Cited by 15 publications

(18 citation statements)

References 183 publications

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“…With respect to taxanes, overexpression of drug efflux pumps and mutations in ␤-tubulin have been implicated as mechanisms that enable cancer cells to adapt to and survive taxane inhibition (Greenberger and Sampath, 2006). Our panel of DU145 cells up-regulated Pgp in response to selection with both paclitaxel and docetaxel.…”

Section: Discussionmentioning

confidence: 94%

“…With respect to taxanes, several mechanisms of inherent or acquired resistance have been implicated in their limited activity in prostate cancer (Greenberger and Sampath, 2006). Included among these resistance mechanisms are altered expression of drug efflux pumps and qualitative changes in the microtubules themselves, which may affect drug-target interactions.…”

Section: Introductionmentioning

confidence: 99%

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Telomere and Microtubule Targeting in Treatment-Sensitive and Treatment-Resistant Human Prostate Cancer Cells

Zhang¹,

Suer²,

Livák³

et al. 2012

Mol Pharmacol

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Modulating telomere dynamics may be a useful strategy for targeting prostate cancer cells, because they generally have short telomeres. Because a plateau has been reached in the development of taxane-based treatments for prostate cancer, this study was undertaken to evaluate the relative efficacy of targeting telomeres and microtubules in taxane-sensitive, taxane-resistant, androgen-sensitive, and androgen-insensitive prostate cancer cells. Paclitaxel-and docetaxel-resistant DU145 cells were developed and their underlying adaptive responses were evaluated. Telomere dynamics and the effects of targeting telomeres with sodium meta-arsenite (KML001) (an agent undergoing early clinical trials), including combinations with paclitaxel and docetaxel, were evaluated in parental and drug-resistant cells. The studies were extended to androgensensitive LNCaP cells and androgen-insensitive LNCaP/C81 cells. Both P-glycoprotein (Pgp)-dependent and non-Pgp-dependent mechanisms of resistance were recruited within the same population of DU145 cells with selection for drug resistance. Wild-type DU145 cells have a small side population (SP) (0.4 -1.2%). The SP fraction increased with increasing drug resistance, which was correlated with enhanced expression of Pgp but not breast cancer resistance protein. Telomere dynamics remained unchanged in taxane-resistant cells, which retained sensitivity to KML001. Furthermore, KML001 targeted SP and non-SP fractions, inducing DNA damage signaling in both fractions. KML001 induced telomere erosion, decreased telomerase gene expression, and was highly synergistic with the taxanes in wild-type and drug-resistant DU145 cells. This synergism extended to androgen-sensitive and androgen-insensitive LNCaP cells under basal and androgen-deprived conditions. These studies demonstrate that KML001 plus docetaxel and KML001 plus paclitaxel represent highly synergistic drug combinations that should be explored further in the different disease states of prostate cancer.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Telomere and Microtubule Targeting in Treatment-Sensitive and Treatment-Resistant Human Prostate Cancer Cells

Zhang¹,

Suer²,

Livák³

et al. 2012

Mol Pharmacol

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“…Five of them are as follows: (i) there can be alterations to membrane lipids, which would give rise to compartmentalization and prevent the passive diffusion of paclitaxel. (ii) Point mutation occurs at the tubulin gene site (Greenberger & Sampath 2006, Ganguly et al 2010). (iii) TLR4 negatively regulates paclitaxel chemotherapy by increasing transcriptional factors and gene inductions (e.g.…”

Section: B-tubulinmentioning

confidence: 99%

The potential role of miRNAs and exosomes in chemotherapy in ovarian cancer

Alharbi

Zúñiga

Elfeky

et al. 2018

Endocrine-Related Cancer

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Chemoresistance is one of the major obstacles in the treatment of cancer patients. It poses a fundamental challenge to the effectiveness of chemotherapy and is often linked to relapse in patients. Chemoresistant cells can be identified in different types of cancers; however, ovarian cancer has one of the highest rates of chemoresistance-related relapse (50% of patients within 5 years). Resistance in cells can either develop through prolonged cycles of treatment or through intrinsic pathways. Mechanistically, the problem of drug resistance is complex mainly because numerous factors are involved, such as overexpression of drug efflux pumps, drug inactivation, DNA repair mechanisms and alterations to and/or mutations in the drug target. Additionally, there is strong evidence that circulating miRNAs participate in the development of chemoresistance. Recently, miRNAs have been identified in exosomes, where they are encapsulated and hence protected from degradation. These miRNAs within exosomes (exo-miRNAs) can regulate

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“…Ursäch-lich könnte eine niedrige Affinität gegenüber dem ATP-abhängigen Medikamentenefflux P-Glykoprotein (P-gp) sein, welchem eine mögliche Verantwortung für die Docetaxel-Resistenz zugeschrieben wird [15,31].…”

Section: Cabazitaxelunclassified

Rolle der Chemotherapie beim kastrationsresistenten Prostatakarzinom

Santis

Bachner

2012

Urologe

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Chemotherapy options for the treatment of metastatic castration-resistant prostate cancer (CRPC) have been very limited for many decades. Until 2004, only mitoxantrone was approved, providing palliation, but no survival benefit. With the introduction of docetaxel, the landscape of chemotherapy for CRPC changed substantially. Prednisone and three-weekly docetaxel showed an overall survival (OS) benefit compared to mitoxantrone plus prednisone, in addition to a significant improvement of quality of life and pain reduction. Further strategies to treat CRPC with chemotherapy include reinduction with docetaxel in responding patients and the use of cabazitaxel, a novel semi-synthetic microtubule inhibitor, in the docetaxel-refractory population. This review article is meant to guide physicians through the optimal use of chemotherapy in CRPC patients in daily clinical practice.

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Resistance To Taxanes

Cited by 15 publications

References 183 publications

Telomere and Microtubule Targeting in Treatment-Sensitive and Treatment-Resistant Human Prostate Cancer Cells

Telomere and Microtubule Targeting in Treatment-Sensitive and Treatment-Resistant Human Prostate Cancer Cells

The potential role of miRNAs and exosomes in chemotherapy in ovarian cancer

Rolle der Chemotherapie beim kastrationsresistenten Prostatakarzinom

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