根據(jù)PDB文件1nkp而構(gòu)建出c-Myc(紅色)與Max(藍色)和DNA形成的復(fù)合物的結(jié)構(gòu),。圖片來自維基共享資源,。
根據(jù)2012年3月9日發(fā)表在Journal of Experimental Medicine期刊上的一篇研究論文,，抑制一種大量存在的促進生長的蛋白能夠?qū)е氯幮匀橄侔┫恕?/p>
三陰性乳腺癌(triple-negative breast tumor)缺乏其他類型乳腺癌中存在的所有已知的可以作為治療靶標(biāo)的生長受體,，這樣也就使得它成為乳腺癌中最難治療的疾病亞型?；忌线@種癌癥的病人往往有著更短的無疾病存活期,，而且腫瘤在他們身上也容易更早地復(fù)發(fā),。
如今，Andrei Goga和同事們發(fā)現(xiàn)三陰性乳腺癌表達高水平的促進生長的MYC蛋白,。MYC活性是這些侵襲性腫瘤生長所必需的,，因而阻斷一種MYC協(xié)作性蛋白(MYC-cooperating protein)，即CDK,，導(dǎo)致小鼠中三陰性乳腺癌萎縮。
歸納在一起,，這些結(jié)果鑒定出一種新的潛在性靶標(biāo)用于治療三陰性乳腺癌。(生物谷：towersimper編譯)
doi:10.1084/jem.20111512
PMC:
PMID:
MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition
Dai Horiuchi, Leonard Kusdra, Noelle E. Huskey, Sanjay Chandriani, Marc E. Lenburg, Ana Maria Gonzalez-Angulo, Katelyn J. Creasman, Alexey V. Bazarov, James W. Smyth, Sarah E. Davis, Paul Yaswen, Gordon B. Mills, Laura J. Esserman, and Andrei Goga
Estrogen, progesterone, and HER2 receptor-negative triple-negative breast cancers encompass the most clinically challenging subtype for which targeted therapeutics are lacking. We find that triple-negative tumors exhibit elevated MYC expression, as well as altered expression of MYC regulatory genes, resulting in increased activity of the MYC pathway. In primary breast tumors, MYC signaling did not predict response to neoadjuvant chemotherapy but was associated with poor prognosis. We exploit the increased MYC expression found in triple-negative breast cancers by using a synthetic-lethal approach dependent on cyclin-dependent kinase (CDK) inhibition. CDK inhibition effectively induced tumor regression in triple-negative tumor xenografts. The proapoptotic BCL-2 family member BIM is up-regulated after CDK inhibition and contributes to this synthetic-lethal mechanism. These results indicate that aggressive breast tumors with elevated MYC are uniquely sensitive to CDK inhibitors.
