Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Trends Microbiol. 2018 Feb;26(2):158-168. doi: 10.1016/j.tim.2017.07.007. Epub 2017 Aug 17.
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.
人乳头瘤病毒（HPV）引起的癌症预计在未来几十年仍将是全球主要的健康问题。HPV 阳性癌细胞的生长依赖于病毒 E6 和 E7 癌基因的持续表达，这些癌基因与尚未明确的细胞改变协同作用。E6/E7 是有吸引力的治疗靶点，因为 E6/E7 抑制可迅速诱导 HPV 阳性癌细胞衰老。这种细胞反应与抑癌基因 p53 和 pRb 通路的重建以及致衰老的 mTOR 信号相关。针对 E6/E7 的治疗策略可能会受到 HPV 阳性缺氧癌细胞的严重阻碍，因为这些细胞会下调 E6/E7，但通过缺氧诱导的 mTOR 损伤来逃避衰老。因此，有前景的 E6/E7 抑制剂可能会受益于与针对缺氧肿瘤细胞的治疗策略相结合。
