biomarker predicting sensitivity (or resistance) to taxanes
 

Needs to be tested in large numbers of patients to confirm, but promising.

One of the cell lines used in the study was SKBR3, WHICH IS her2+ER-PR-

ABSTRACT: Cytoskeleton and paclitaxel sensitivity in breast cancer: The role of ?-tubulins [International Journal of Cancer]
The antineoplastic effect of paclitaxel is mainly related to its ability to bind the ? subunit of tubulin, thus preventing tubulin chain depolarization and inducing apoptosis. The relevance of the Class I ?-tubulin characteristics have also been confirmed in the clinical setting where mutations of paclitaxel-binding site of ?-tubulin Class I have been related to paclitaxel resistance in non small cell lung and ovarian cancers. In the present study, we verified the hypothesis of a relationship between molecular alterations of ?-tubulin Class I and paclitaxel sensitivity in a panel of breast cell lines with different drug IC50. The Class I ?-tubulin gene cDNA has been sequenced detecting heterozygous missense mutations (exon 1 and 4) only in MCF-7 and SK-BR-3 lines. Furthermore, the expression (at both mRNA and protein level) of the different isotypes have been analyzed demonstrating an association between low cell sensitivity to paclitaxel and Class III ?-tubulin expression increasing. Antisense oligonucleotide (ODN) experiments confirmed that the inhibition of Class III ?-tubulin could at least partially increase paclitaxel-chemosensitivity. The hypothesis of a relationship between ?-tubulin tumor expression and paclitaxel clinical response has been finally verified in a series of 92 advanced breast cancer patients treated with a first line paclitaxel-based chemotherapy. Thirty-five percent (95% CI: 45-31) of patients with high Class III ?-tubulin expression showed a disease progression vs. only 7% of patients with low expression (35% vs. 7%, p < 0.002). Our study suggests that Class III ?-tubulin tumor expression could be considered a predictive biomarker of paclitaxel-clinical resistance for breast cancer patients.

So, is this saying that there might be a preliminary implication that ER+ bc cell lines (MCF-7) and a Her2+ cell line are sensitive to taxanes. This would make sense (even though the Her2+ line here is also ER/PR -) as there was a real study on node positive bc using taxol (real women) presented at San Antonio that showed that using taxol greatly reduces the chance of recurrence in Her2+ women REGARDLESS of hormone status.


However, the same study showed that taxanes do relatively nothing to node positive women who are only hormone positive and not Her2+ as well. However, MCF-7 is a line that is sensitive to alpha and beta estrogens (and many Her2+ women who are hormone positive tend to be beta+ so.... that may be the responsive part of this cell line.

This is a great article Lani. Thanks for posting it as it has held true to form in a real life study.