Resistance to chemotherapeutics is a common adverse event in the treatment of breast cancer. The chemotherapeutic agent docetaxel is in common use as a chemotherapeutic, but resistance to treatment after long exposure is a common downfall of docetaxel. Overcoming resistance to well used chemotherapeutic agents would be a boon to the fight against cancer.
A recent article found in PLoS ONE investigates the effect of treatment of docetaxel-resistant MCF-7 breast cancer cells with microtubule destabilizing agents, in the hope of overcoming taxane-resistance. The work reported that taxane-resistant MCF-7 cells were still resistant to treatment with vinca alkaloids, but colchicine binding site agents were more potent in the docetaxel-resistant MCF-7 cells than in wild-type MCF-7 cells.
In addition to colchicine, other colchicine binding site agents also showed the same pattern against wild-type and docetaxel resistant MCF-7 cells. One such colchicine binding site agent exhibiting this property was 2-methoxyestradiol.
However, the vinka alkaloids vinorelbine and vinblastine lost potency against the docetaxel-resistant MCF-7 cells. Both of these vinka alkaloids showed about a 3-6 times decrease in potency between wild-type and taxane-resistant cells. The overall potency is still sub-micromolar in the cytotoxicity assay.
In all, colchicine binding site agents may be suitable for co-administration with docetaxel to overcome drug-resistance mechanisms.
These microtubule interacting compounds are available from LKT Laboratories, Inc. for your research needs.
Wang RC, Chen X Parissenti AM, Joy AA, Tuszynski J, Brindley DN, et al. (2017) “Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.” PLoS ONE 12(8): e0182400. https://doi.org/10.1371/journal.pone.0182400