Taxane resistance in breast cancer: mechanisms, predictive biomarkers and circumvention strategies.

Murray, S.; Briasoulis, E.; Linardou, H.; Bafaloukos, D.; Papadimitriou, C.

doi:10.1016/j.ctrv.2012.02.011

Cited by 261Cancer Treatment and PharmacologyDrug Transport and Resistance MechanismsBreast Cancer Treatment Studies

Taxane resistance in breast cancer: mechanisms, predictive biomarkers and circumvention strategies.

Murray, S., Briasoulis, E., Linardou, H., Bafaloukos, D., Papadimitriou, C.·2012·Cancer Treatment Reviews

DOI 10.1016/j.ctrv.2012.02.011

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Abstract

Background Taxanes are established in the treatment of metastatic breast cancer (MBC) and early breast cancer (EBC) as potent chemotherapy agents. However, their therapeutic usefulness is limited by de-novo refractoriness or acquired resistance, which are common drawbacks to most anti-cancer cytotoxics. Considering that the taxanes will remain principle chemotherapeutic agents for the treatment of breast cancer, we reviewed known mechanisms of resistance in with an outlook of optimizing their clinical use.Methods We searched the PubMed and MEDLINE databases for articles (from inception through to 9th January 2012; last search 10/01/2012) and journals known to publish information relevant to taxane chemotherapy. We imposed no language restrictions. Search terms included: cancer, breast cancer, response, resistance, taxane, paclitaxel, docetaxel, taxol. Due to the possibility of alternative mechanisms of resistance all combination chemotherapy treated data sets were removed from our overview.Results Over-expression of the MDR-1 gene product Pgp was extensively studied in vitro in association with taxane resistance, but data are conflicting. Similarly, the target components microtubules, which are thought to mediate refractoriness through alterations of the expression pattern of tubulins or microtubule associated proteins and the expression of alternative tubulin isoforms, failed to confirm such associations. Little consensus has been generated for reported associations between taxane-sensitivity and mutated p53, or taxane-resistance and overexpression of Bcl-2, Bcl-xL or NFkB. In contrary sufficient in vitro data support an association of spindle assembly checkpoint (SAC) defects with resistance. Clinical data have been limited and inconsistent, which relate to the variety of methods used, lack of standardization of cut-offs for quantitation, differences in clinical endpoints measured and in methods of tissue collection preparation and storage, and study/patient heterogeneity. The most prominent finding is that pharmaceutical down-regulation of HER-2 appears to reverse the taxane resistance.Conclusions Currently no valid practical biomarkers exist that can predict resistance to the taxanes in breast cancer supporting the principle of individualized cancer therapy. The incorporation of several biomarker analyses into prospectively designed studies in this setting are needed.

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Resistance to paclitaxel and docetaxel often develops.
“While paclitaxel and docetaxel are front-line chemotherapeutics for treating breast, prostate and nasopharyngeal carcinomas, resistance to these compounds often develops (Murray et al., 2012).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Murray et al., 2012
Paclitaxel and docetaxel are front-line chemotherapeutics for treating breast, prostate and nasopharyngeal carcinomas.
“While paclitaxel and docetaxel are front-line chemotherapeutics for treating breast, prostate and nasopharyngeal carcinomas, resistance to these compounds often develops (Murray et al., 2012).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Murray et al., 2012

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Authors: Murray, S., Briasoulis, E., Linardou, H., Bafaloukos, D., & Papadimitriou, C.
Affiliations: University of Ioannina (GR)
Metropolitan Hospital (GR)
National and Kapodistrian University of Athens (GR)
Corresponding author: Murray, S.
ORCID: Briasoulis, E.
Linardou, H.
Papadimitriou, C.
Venue: Cancer Treatment Reviews
Publisher: Elsevier BV
Published: 2012-11
Volume: 38
Issue: 7
Pages: 890-903
ISSN: 0305-7372 (ISSN-L)
DOI: 10.1016/j.ctrv.2012.02.011
OpenAlex: W1978728170
Cited by: 261
References: 204
Citations by year: 2026: 7 · 2025: 11 · 2024: 18 · 2023: 11 · 2022: 20 · 2021: 20 · 2020: 18 · 2019: 16 · 2018: 25 · 2017: 18 · 2016: 19 · 2015: 33 · 2014: 23 · 2013: 17 · 2012: 3
FWCI: 2.51
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cancer Treatment Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords: taxane resistance, breast cancer, paclitaxel, docetaxel, multidrug resistance protein 1, PGP, microtubules, tubulin isoforms, TP53 mutation, Bcl-2, NF-κB, spindle assembly checkpoint, predictive biomarkers, acquired drug resistance
MeSH terms: Animals, Antineoplastic Agents, Breast Neoplasms, Bridged-Ring Compounds, Female, Humans, Biomarkers, Tumor, Drug Resistance, Neoplasm, ATP Binding Cassette Transporter, Subfamily B, Member 1, Taxoids

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Taxane resistance in breast cancer: mechanisms, predictive biomarkers and circumvention strategies.

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