本期Nature Communications上发表的一项研究报告说，基因TEKT4所发生的遗传变化与对乳腺癌化疗药物紫杉醇(paclitaxel)的抵抗力有关。这些发现揭示了一些类型的乳腺癌患者对紫杉醇的抗药性的一个可能的机制。

    紫杉醇是用来治疗乳腺癌的一种化疗药物，然而这种治疗经常会碰到抗药性。Zhi-Ming Shao、Ke-Da Yu及同事在用紫杉醇治疗前和治疗后对患者的乳腺癌组织进行了测序，发现一些样本在治疗后TEKT4基因变异水平增加。作者指出，这些患者与没有那些变异体的患者相比无病存活率总体上降低。

    TEKT4的蛋白产物已知稳定微管（细胞中对细胞分裂重要的细丝），后者是紫杉醇的作用目标。在实验室的培养细胞中，本文作者发现，变异的TEKT4基因的表达导致对紫杉醇的抗药性增强，并使微管失去稳定性。这些发现为一些类型的乳腺癌患者何以会对紫杉醇产生抗药性提供了一个可能的机制。

Among chemotherapeutic agents, paclitaxel has shown great efficacy against breast cancer. Prediction of paclitaxel response may improve patient outcomes. Here we show, using exome sequencing, that in comparison with pre-treatment biopsies, two TEKT4 germline variations are enriched in post-treatment tumours. We find TEKT4 variations in ~\n10% of an independent cohort of 84 pairs of samples. Tektin4 (encoded by TEKT4) associates closely with tubulin in doublet microtubules and helps stabilize these structures. These two TEKT4 germline variations in a high cis linkage are biologically relevant, as the ectopic expression of variant TEKT4 deregulates the microtubule stability, antagonizes the paclitaxel-induced stabilizing effect of microtubules and increases paclitaxel resistance. Furthermore, TEKT4 germline variations are associated with reduced disease-free survival and overall survival compared with wild-type TEKT4 in patients undergoing paclitaxel-based chemotherapy. Taken together, we reveal a potential mechanism of resistance to paclitaxel through the acquisition of germline variations in breast cancer.