人們常說,，閃電從來不會(huì)兩次擊打同一個(gè)地方，當(dāng)然如果該地方是避雷針除外,。 一則對(duì)小鼠和人的最新研究報(bào)告顯示,，一種叫做UROD（尿卟啉原脫羧酶）的酶，其作用就像是癌細(xì)胞的避雷針,，它會(huì)將放療和化療吸引到病變組織的特定的部位,。
這些發(fā)現(xiàn)表明，UROD（它在本文章中第一次被看作是人類癌癥中的一個(gè)關(guān)鍵性的角色）可幫助降低頭頸部癌癥患者的治療副作用,。頭頸部癌癥是全世界排第8位的最常見的癌癥,。 盡管在最近的幾十年中所取得的諸多進(jìn)展，與當(dāng)前療法有關(guān)的毒性副作用對(duì)許多患者來說已經(jīng)產(chǎn)生了令人失望的后果。 頭頸部腫瘤常常被發(fā)現(xiàn)位于重要器官的附近,，因此,，摧毀病變組織常常是一個(gè)棘手的挑戰(zhàn)，因?yàn)樗鼤?huì)導(dǎo)致威脅生命的各種狀況,。
Emma Ito及其同事在這里顯示,，將UROD作為標(biāo)靶可選擇性地增進(jìn)對(duì)頭頸部腫瘤的放療和化療的功效，同時(shí)也可將其對(duì)正常組織的毒性最小化,。通過將治療聚焦于組織的特別部位,，病人可在不損害治療功效的同時(shí)接受較低劑量的放療和化療藥物。
UROD是一種參與生產(chǎn)一種叫做血紅素分子的酶,，而血紅素對(duì)身體所有器官都是至關(guān)重要的（盡管它在血液,、骨髓和肝臟中最豐富）。血紅素是一類叫做血紅素蛋白（其中包括在血液中攜帶氧氣的蛋白：血紅蛋白）的含鐵蛋白中的主要成分,。在小鼠中,，阻斷UROD基因的表達(dá)可增加癌細(xì)胞的死亡。對(duì)頭頸部癌癥組織樣本的分析披露,，腫瘤中的UROD濃度比正常組織顯著要高,。此外，研究人員確認(rèn),，臨床結(jié)果的改善與病人體內(nèi)較低的UROD水平有關(guān)聯(lián),，提示UROD可被用來預(yù)測(cè)病人對(duì)放療的反應(yīng)。文章的作者希望,，UROD抑制劑將來可與放療和化療共同使用以降低副作用,。（生物谷Bioon.com）
原文出處：
Sci Transl Med Vol. 3, Issue 67, DOI: 10.1126/scitranslmed.3001922
Uroporphyrinogen Decarboxylase Is a Radiosensitizing Target for Head and Neck Cancer
Emma Ito1,2, Shijun Yue2, Eduardo H. Moriyama2, Angela B. Hui2, Inki Kim2, Wei Shi2, Nehad M. Alajez2, Nirmal Bhogal2, GuoHua Li3, Alessandro Datti4,5, Aaron D. Schimmer1,2, Brian C. Wilson1,2, Peter P. Liu3, Daniel Durocher4, Benjamin G. Neel1,2, Brian O’Sullivan6,7, Bernard Cummings6,7, Rob Bristow1,2,6,7, Jeff Wrana4 and Fei-Fei Liu1,2,6,7,*
Head and neck cancer (HNC) is the eighth most common malignancy worldwide, comprising a diverse group of cancers affecting the head and neck region. Despite advances in therapeutic options over the last few decades, treatment toxicities and overall clinical outcomes have remained disappointing, thereby underscoring a need to develop novel therapeutic approaches in HNC treatment. Uroporphyrinogen decarboxylase (UROD), a key regulator of heme biosynthesis, was identified from an RNA interference–based high-throughput screen as a tumor-selective radiosensitizing target for HNC. UROD knockdown plus radiation induced caspase-mediated apoptosis and cell cycle arrest in HNC cells in vitro and suppressed the in vivo tumor-forming capacity of HNC cells, as well as delayed the growth of established tumor xenografts in mice. This radiosensitization appeared to be mediated by alterations in iron homeostasis and increased production of reactive oxygen species, resulting in enhanced tumor oxidative stress. Moreover, UROD was significantly overexpressed in HNC patient biopsies. Lower preradiation UROD mRNA expression correlated with improved disease-free survival, suggesting that UROD could potentially be used to predict radiation response. UROD down-regulation also radiosensitized several different models of human cancer, as well as sensitized tumors to chemotherapeutic agents, including 5-fluorouracil, cisplatin, and paclitaxel. Thus, our study has revealed UROD as a potent tumor-selective sensitizer for both radiation and chemotherapy, with potential relevance to many human malignancies.
