患有最為常見(jiàn)肺癌類型---非小細(xì)胞肺癌(non-small cell lung cancer, NSCLC)---的病人對(duì)包括順鉑(cisplatin)在內(nèi)的化療藥物非常敏感,。根據(jù)于2012年7月26日發(fā)表在Cell Reports期刊上的一篇論文,，研究人員發(fā)現(xiàn)了非小細(xì)胞肺癌對(duì)順鉑作出反應(yīng)相關(guān)的細(xì)胞途徑,。這些研究人揭示一種潛在的生物標(biāo)記物,，它能夠被用來(lái)預(yù)測(cè)這些病人如何對(duì)化療作出反應(yīng),，以及他們的總體預(yù)后結(jié)果,，從而為個(gè)人化治療策略奠定基礎(chǔ),。
人們經(jīng)常順鉑來(lái)非小細(xì)胞肺癌(NSCLC),。但是,，治療效果經(jīng)常是短暫的和無(wú)效的，這是因?yàn)榘┘?xì)胞對(duì)順鉑誘導(dǎo)的細(xì)胞死亡產(chǎn)生抵抗力。為了鑒定哪些因子影響接受順鉑治療的癌細(xì)胞是否會(huì)死亡,，論文通信作者、法國(guó)國(guó)家健康與醫(yī)學(xué)研究院(French National Institute of Health and Medical Research, INSERM)研究員Guido Kroemer和同事們開(kāi)展全基因組篩查,，在這過(guò)程中,，他們干擾來(lái)自NSCLC患者體內(nèi)的細(xì)胞中成千上萬(wàn)個(gè)基因的表達(dá)。他們鑒定出85個(gè)改變藥物療效的因子,，包括一種將維生素B6前體變成有活性的維生素B6的酶,，即吡哆醛激酶(pyridoxal kinase, PDXK)。
在肺癌小鼠模式動(dòng)物中,，服用維生素B6前體能夠加強(qiáng)順鉑的抗腫瘤效果,，能夠促進(jìn)順鉑誘導(dǎo)的多種癌細(xì)胞系死亡，但是這一切必須只在酶PDXK存在時(shí)才如此。再者,，不管NSCLC患者是否接受順鉑治療,，他們當(dāng)中表達(dá)高水平PDXK的患者要比表達(dá)低水平PDXK的患者擁有較高的存活率。
總之,，這些發(fā)現(xiàn)指出酶PDXK是一種容易監(jiān)測(cè)的潛在生物標(biāo)記物,，能夠被用來(lái)預(yù)測(cè)NSCLC患者對(duì)順鉑治療作出的反應(yīng)和他們的總體治療結(jié)果。(生物谷：Bioon.com)
本文編譯自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.
