期刊
TRENDS IN MICROBIOLOGY
卷 26, 期 2, 页码 158-168出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.tim.2017.07.007
关键词
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资金
- Wilhelm Sander-Stiftung [2015.137.1]
- Deutsche Krebshilfe [112132]
Human papillomavirus (HPV)-induced cancers are expected to remain a major health problem worldwide for decades. The growth of HPV-positive cancer cells depends on the sustained expression of the viral E6 and E7 oncogenes which act in concert with still poorly defined cellular alterations. E6/E7 constitute attractive therapeutic targets since E6/E7 inhibition rapidly induces senescence in HPV-positive cancer cells. This cellular response is linked to the reconstitution of the antiproliferative p53 and pRb pathways, and to prosenescent mTOR signaling. Hypoxic HPV-positive cancer cells could be a major obstacle for treatment strategies targeting E6/E7 since they downregulate E6/E7 but evade senescence through hypoxia-induced mTOR impairment. Prospective E6/E7 inhibitors may therefore benefit from a combination with treatment strategies directed against hypoxic tumor cells.
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