Mechanisms of Taxane Resistance

Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

Farnesyltransferase inhibitors reverse taxane resistance.

The combination of farnesyltransferase inhibitors (FTIs) and taxanes has been shown to result in potent antiproliferative and antimitotic synergy. Recent phase I and II clinical trials have shown that this combination shows clinical activity in taxane-refractory or taxane-resistant cancer patients. To understand the mechanism behind these clinical observations, we used a cancer cell model of pa...

Taxane resistance in breast cancer

Despite recent progress in the treatment of breast cancer, disease recurrence remains a major issue to curative therapy. One of the major clinical issues is the development of drug resistance. Taxane resistance is a big challenge because taxanes, either alone or in combination, is the first-line regimens for treating breast cancer. A hierarchy of resistant mechanisms are responsible for taxane ...

The taccalonolides: microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms.

The taccalonolides are a class of structurally and mechanistically distinct microtubule-stabilizing agents isolated from Tacca chantrieri. A crucial feature of the taxane family of microtubule stabilizers is their susceptibility to cellular resistance mechanisms including overexpression of P-glycoprotein (Pgp), multidrug resistance protein 7 (MRP7), and the betaIII isotype of tubulin. The abili...

ERG induces taxane resistance in castration-resistant prostate cancer

Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in in vitro and in vivo models of CRPC is associated with decreased sensitivity to taxanes. ERG affe...