Hematologic β-Tubulin VI Isoform Exhibits Genetic Variability That Influences Paclitaxel Toxicity

Leandro‐García, Luis Javier; Leskelä, Susanna; Inglada-Pérez, Lucía; Landa, Iñigo; Cubas, Aguirre A. de; Maliszewska, Agnieszka; Comino-Méndez, Iñaki; Letón, Rocío; Gómez-Graña, Álvaro; Torres-Ruíz, Raúl; Ramı́rez, Juan Carlos; Álvarez, Sara; Rivera, José; Martı́nez, Constantino; Lozano, Marı́a Luisa; Cascón, Alberto; Robledo, Mercedes; Rodríguez‐Antona, Cristina

doi:10.1158/0008-5472.can-11-2861

Cited by 25 publications

(17 citation statements)

References 30 publications

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“…For instance, differential isotype expression has been observed in various cancers (reviewed in Parker et al, 2014) and could be involved in rendering these cancers more resistant to therapeutic drugs (Kamath et al, 2005;Leandro-Garcia et al, 2012;Yang et al, 2016).…”

Section: Functions Of the Tubulin Code In Health And Diseasementioning

confidence: 99%

The tubulin code at a glance

Gadadhar

Bodakuntla

Natarajan

et al. 2017

Journal of Cell Science

210

227

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Microtubules are key cytoskeletal elements of all eukaryotic cells and are assembled of evolutionarily conserved α-tubulin-β-tubulin heterodimers. Despite their uniform structure, microtubules fulfill a large diversity of functions. A regulatory mechanism to control the specialization of the microtubule cytoskeleton is the 'tubulin code', which is generated by (i) expression of different α-and β-tubulin isotypes, and by (ii) post-translational modifications of tubulin. In this Cell Science at a Glance article and the accompanying poster, we provide a comprehensive overview of the molecular components of the tubulin code, and discuss the mechanisms by which these components contribute to the generation of functionally specialized microtubules.

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Section: Functions Of the Tubulin Code In Health And Diseasementioning

confidence: 99%

The tubulin code at a glance

Gadadhar

Bodakuntla

Natarajan

et al. 2017

Journal of Cell Science

210

227

View full text Add to dashboard Cite

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“…Patients carrying these variants may be at decreased risk of developing paclitaxel-induced neurotoxicity [71]. Similarly, a polymorphism in TUBB1 may modulate a patient’s risk of taxane-induced thrombocytopenia [72], however, replication of these associations has not yet been attempted to our knowledge.…”

Section: Pharmacogeneticsmentioning

confidence: 99%

Pharmacogenetics, Enzyme Probes and Therapeutic drug Monitoring as Potential Tools for Individualizing Taxane Therapy

2013

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The taxanes are a class of chemotherapeutic agents that are widely used in the treatment of various solid tumors. Although taxanes are highly effective in cancer treatment, their use is associated with serious complications attributable to large interindividual variability in pharmacokinetics and a narrow therapeutic window. Unpredictable toxicity occurrence necessitates close patient monitoring while on therapy and adverse effects frequently require decreasing, delaying or even discontinuing taxane treatment. Currently, taxane dosing is based primarily on body surface area, ignoring other factors that are known to dictate variability in pharmacokinetics or outcome. This article discusses three potential strategies for individualizing taxane treatment based on patient information that can be collected before or during care. The clinical implementation of pharmacogenetics, enzyme probes or therapeutic drug monitoring could enable clinicians to personalize taxane treatment to enhance efficacy and/or limit toxicity.

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“…A previously reported population of 361 healthy individuals was used for genotype frequency comparisons. Details of recruitment, collection, and analysis are reported separately (Leandro-García et al, 2012).…”

Section: Patients and Clinical Datamentioning

confidence: 99%

The beta 1 tubulin R307H single nucleotide polymorphism is associated with treatment failures in immune thrombocytopenia (ITP)

et al. 2012

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Summary Predictive biomarkers are needed in ITP. Single nucleotide polymorphisms (SNPs) in beta 1 tubulin are potential candidates, as beta 1 tubulin is integral for platelet production and function, and SNPs in beta 1 tubulin have been associated with distinct phenotypes in platelets. We investigated the most prevalent beta 1 tubulin SNP (R307H) as a biomarker in patients with ITP via a retrospective chart review. Allelic frequencies between a group of 191 ITP patients and a healthy control group showed no difference, suggesting no direct etiologic role for the SNP in ITP. However, over similar periods of follow-up, both heterozygote and homozygote minor allele ITP patients were treated with significantly more treatment modalities and had significantly higher risk of failure to immune-modulatory therapies (RR=1.5, 95%CI=1.1–2.1;p=0.01); with rituximab, in particular, ITP patients with the SNP experienced a 58% failure rate (RR=1.6, 95%CI=1.03–2.5; p=0.04). Analysis of the absolute immature platelet fraction (A-IPF) as a marker of platelet production showed that SNP patients had significantly higher median A-IPFs compared to non-SNP patients when complete responses were achieved using immune modulatory therapies. The data suggest that the beta 1 tubulin R307H SNP has potential for use as a biomarker in ITP and may affect platelet turnover.

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Hematologic β-Tubulin VI Isoform Exhibits Genetic Variability That Influences Paclitaxel Toxicity

Cited by 25 publications

References 30 publications

The tubulin code at a glance

The tubulin code at a glance

Pharmacogenetics, Enzyme Probes and Therapeutic drug Monitoring as Potential Tools for Individualizing Taxane Therapy

The beta 1 tubulin R307H single nucleotide polymorphism is associated with treatment failures in immune thrombocytopenia (ITP)

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