Cancer: Gene variants associated with drug resistance

Genetic variations in the gene TEKT4 are associated with resistance to the breast cancer chemotherapy drug, paclitaxel, reports a study published in Nature Communications this week. These findings highlight a possible mechanism for resistance to paclitaxel in a subset of breast cancer patients.

Paclitaxel is a chemotherapeutic agent used to treat breast cancer; however, this treatment is often met with drug resistance. Zhi-Ming Shao, Ke-Da Yu, and colleagues sequenced breast cancer tissue from patients both before and after paclitaxel treatment and found that some samples had increased levels of TEKT4 gene variation after treatment. The authors note that these patients had reduced overall disease free survival compared to patients without the variants.

The protein product of TEKT4 is known to stabilise microtubules - filaments in cells that are important for cell division, which are the target of paclitaxel. In cultured cells in the laboratory, the authors showed that expression of the variant TEKT4 gene resulted in enhanced resistance to paclitaxel and destabilised microtubules. These findings provide a possible mechanism for how a subset of breast cancer patients may develop resistance to paclitaxel.