The HPV E6/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets
2017; Elsevier BV; Volume: 26; Issue: 2 Linguagem: Inglês
10.1016/j.tim.2017.07.007
ISSN1878-4380
AutoresKarin Hoppe‐Seyler, Felicitas Bossler, Julia A. Braun, Anja L. Herrmann, Felix Hoppe‐Seyler,
Tópico(s)Cancer-related Molecular Pathways
ResumoHuman 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.
Referência(s)