Cell Reports：新标记物PDXK预测非小细胞肺癌化疗疗效

患有最为常见肺癌类型---非小细胞肺癌(non-small cell lung cancer, NSCLC)---的病人对包括顺铂(cisplatin)在内的化疗药物非常敏感。根据于2012年7月26日发表在Cell Reports期刊上的一篇论文，研究人员发现了非小细胞肺癌对顺铂作出反应相关的细胞途径。这些研究人揭示一种潜在的生物标记物，它能够被用来预测这些病人如何对化疗作出反应，以及他们的总体预后结果，从而为个人化治疗策略奠定基础。

人们经常顺铂来非小细胞肺癌(NSCLC)。但是，治疗效果经常是短暂的和无效的，这是因为癌细胞对顺铂诱导的细胞死亡产生抵抗力。为了鉴定哪些因子影响接受顺铂治疗的癌细胞是否会死亡，论文通信作者、法国国家健康与医学研究院(French National Institute of Health and Medical Research, INSERM)研究员Guido Kroemer和同事们开展全基因组筛查，在这过程中，他们干扰来自NSCLC患者体内的细胞中成千上万个基因的表达。他们鉴定出85个改变药物疗效的因子，包括一种将维生素B6前体变成有活性的维生素B6的酶，即吡哆醛激酶(pyridoxal kinase, PDXK)。

在肺癌小鼠模式动物中，服用维生素B6前体能够加强顺铂的抗肿瘤效果，能够促进顺铂诱导的多种癌细胞系死亡，但是这一切必须只在酶PDXK存在时才如此。再者，不管NSCLC患者是否接受顺铂治疗，他们当中表达高水平PDXK的患者要比表达低水平PDXK的患者拥有较高的存活率。

总之，这些发现指出酶PDXK是一种容易监测的潜在生物标记物，能够被用来预测NSCLC患者对顺铂治疗作出的反应和他们的总体治疗结果。

本文编译自New biomarker for common lung cancer predicts responses to chemotherapy

doi: 10.1016/j.celrep.2012.06.017
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Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

Lorenzo Galluzzi, Ilio Vitale, Laura Senovilla et al.

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.