近日,，瑞典卡羅琳學(xué)院的研究人員發(fā)現(xiàn)用于治療晚期腎癌和肝癌的藥物多吉美（sorafenib）對(duì)多發(fā)性骨髓瘤（multiple myeloma）同樣有效,。相關(guān)論文于9月4日發(fā)表在國(guó)際期刊Cancer Research上。
多發(fā)性骨髓瘤是白血病的一種,，通常被認(rèn)為是不治之癥,，只在成年人中發(fā)病，且在40歲之前發(fā)病率低,，患者年齡大多在60歲以上,。骨髓瘤細(xì)胞存在于骨髓中，它的出現(xiàn)破壞了血細(xì)胞的正常產(chǎn)生,?；颊甙Y狀是骨質(zhì)疏松，易骨折,，同時(shí)因脊柱縮短背部產(chǎn)生劇痛,。其他癥狀有貧血、乏力,、腎衰竭,、易發(fā)生感染等。
此項(xiàng)研究的領(lǐng)導(dǎo)者Theocharis Panaretakis說(shuō),，"近些年開(kāi)發(fā)出的藥物,，如硼替佐米，已經(jīng)提高了多發(fā)性骨髓瘤患者的生存率,。但是由于不良的治療反應(yīng),、抗藥性等，幾乎所有的患者都出現(xiàn)復(fù)發(fā),，因此不得不尋找更好的治療方法,。"
研究者使用的是患者的骨髓瘤細(xì)胞和小鼠的細(xì)胞系。這些患者來(lái)自卡羅林斯卡大學(xué)醫(yī)院,，在此之前基本未做任何治療,。研究發(fā)現(xiàn)多吉美可通過(guò)抑制Mcl-1的蛋白表達(dá)水平促進(jìn)人骨髓瘤細(xì)胞的凋亡。在骨髓瘤細(xì)胞對(duì)硼替佐米產(chǎn)生耐受之后,，多吉美仍可發(fā)揮作用,。隨后小鼠體內(nèi)的實(shí)驗(yàn)結(jié)果也發(fā)現(xiàn)，多吉美可以阻止或延緩多發(fā)性骨髓瘤的病程,。因此,，研究者認(rèn)為多吉美可以與其他藥物聯(lián)合使用治療多發(fā)性骨髓瘤。（生物谷Bioon.com）
編譯自Possible new therapy for the treatment of myeloma
doi:10.1158/0008-5472.CAN-12-0658
PMC:
PMID:
Sorafenib has potent anti-tumor activity in multiple myeloma in vitro, ex vivo and in vivo, in the 5T33MM mouse model
Pedram Kharaziha1, Hendrik De Raeve2, Charlotte Fristedt3, Qiao Li1, Astrid Gruber4, Per Johnsson1, Georgia Kokaraki1, Maria Panzar1, Edward Laane5, Anders Osterborg6, Boris Zhivotovsky7, Helena Jernberg-Wiklund3, Dan Grander1, Fredrik Celsing4, Magnus Bjorkholm4, Karin Vanderkerken8, and Theocharis Panaretakis
Multiple Myeloma (MM) is a B-cell malignancy characterized by the expansion of clonal plasma blasts/plasma cells within the bone marrow (BM) that relies on multiple signaling cascades, including tyrosine kinase activated pathways, to proliferate and evade cell death. Despite emerging new treatment strategies, MM remains at present incurable. Thus, novel approaches targeting several signaling cascades by using the multi-tyrosine kinase inhibitor (TKI), sorafenib, seems a promising treatment approach for MM. Here, we demonstrate that sorafenib induces cell death in MM cell lines and in CD138+ enriched primary MM patient samples in a caspase-dependent and independent manner. Furthermore, sorafenib has a strong anti-tumoral and anti-angiogenic activity in the 5T33MM mouse model leading to increased overall survival. MM cells undergo autophagy in response to sorafenib and inhibition of this cytoprotective pathway potentiated the efficacy of this TKI. Mcl-1, a survival factor in MM, is downregulated at the protein level by sorafenib allowing for the execution of cell death, since ectopic overexpression of this protein protects MM cells. Concomitant targeting of Mcl-1 by sorafenib and of Bcl-2/Bcl-xL by the antagonist ABT737 improves the efficacy of sorafenib in MM cell lines and CD138+ enriched primary cells in the presence of BM stromal cells. Altogether, our data support the use of sorafenib as a novel therapeutic modality against human MM and its efficacy maybe potentiated in combination with ABT737.
