Impact of Membrane Drug Transporters on Resistance to Small-Molecule Tyrosine Kinase Inhibitors

Neul, Claudia; Schaeffeler, Elke; Sparreboom, Alex; Laufer, Stefan; Schwab, Matthias; Nies, Anne T.

doi:10.1016/j.tips.2016.08.003

Cited by 73 publications

(92 citation statements)

References 192 publications

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“…Such agents would ideally have high potency, high specificity, low drug-drug interaction potential, intrinsic antitumor properties, favorable pharmaceutical properties, and nonoverlapping toxicity profiles. We hypothesized that the class of TKIs is of particular interest in this context, as these agents have many of the above features, and several members of the class have been found to potently inhibit various drug transporters (43). The ultimate identification of nilotinib as an inhibitor of OATP1B2, without being itself a transported substrate, is consistent with a recent report suggesting…”

Section: Oatp1b2 As a Putative Paclitaxel Transporter In Mouse Neuronssupporting

confidence: 80%

OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity

Leblanc¹,

Sprowl²,

Alberti³

et al. 2018

Journal of Clinical Investigation

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Section: Oatp1b2 As a Putative Paclitaxel Transporter In Mouse Neuronssupporting

confidence: 80%

OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity

Leblanc¹,

Sprowl²,

Alberti³

et al. 2018

Journal of Clinical Investigation

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“…“Molecular targeted therapies” are used in the treatment of many cancers as first-line therapy (Neul et al, 2016). The first tyrosine kinase inhibitor (TKI) approved for the treatment of CML was imatinib mesylate (Cierpicki and Grembecka, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The first tyrosine kinase inhibitor (TKI) approved for the treatment of CML was imatinib mesylate (Cierpicki and Grembecka, 2015). Since then, over 3000 novel agents inhibiting diverse protein kinases are currently being explored preclinically and, at present, more than 130 novel TKIs are being evaluated in oncological clinical trials (Neul et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

A Pyrazolo[3,4-d]pyrimidine Compound Reduces Cell Viability and Induces Apoptosis in Different Hematological Malignancies

et al. 2016

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Molecular targeted therapies are based upon drugs acting on tumors by interfering with specific targets involved in growth and spread of cancer. Many targeted therapies were approved by Food and Drug Administration as standard treatment, others were introduced into preclinical or clinical studies on hematological malignancies (HMs). The development of drug-resistance in some HMs and the lack of effective treatments in other ones emphasized the need for searching new molecular targets and therapeutic agents. The aim of this study was to evaluate the effects of 4c pyrazolo[3,4-d]pyrimidine compound, a Src inhibitor, on lymphoid and myeloid neoplasms. Here, we demonstrated its ability to reduce cell viability, induce apoptosis and cell cycle arrest in lymphoid cell lines such as Jurkat, SKMM1, Derl-2/7, and myeloid cell lines, such as Jurl-MK1. Moreover, we reported a high expression of a Src kinase, Fyn, in these cell lines compared to healthy subjects. This study was a starting point to investigate 4c pyrazolo[3,4-d]pyrimidine compound as a drug for HMs and Src kinases as its potential molecular targets.

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“…DNA methylation, histone modifications, or miRNAs; and (d) regulatory factors, e.g. transcriptional, posttranscriptional, or posttranslational regulation [4].…”

Section: Clinical Consequences Of Interindividual Variability Of Tranmentioning

confidence: 99%