Redox‐sensitive signalling pathways regulated by human papillomavirus in HPV‐related cancers

Abstract

High-risk human papillomavirus (HR-HPV) chronic infection is associated with the induction of different HPV-related cancers, such as cervical, anus, vaginal, vulva, penis and oropharynx. HPV-related cancers have been related to oxidative stress (OS), where OS has a significant role in cancer development and maintenance.Surgical resection is the treatment of choice for localised HPV-related cancers; however, these malignancies commonly progress to metastasis. In advanced stages, systemic therapies are the best option against HPV-related cancers. These therapies include cytokine therapy or a combination of tyrosine kinase inhibitors with immunotherapies. Nevertheless, these strategies are still insufficient. Cell redoxsensitive signalling pathways have been poorly studied, although they have been associated with the development and maintenance of HPV-related cancers. In this review, we analyse the known alterations of the following redox-sensitive molecules and signalling pathways by HR-HPV in HPV-related cancers: MAPKs, Akt/TSC2/ mTORC1, Wnt/β-Cat, NFkB/IkB/NOX2, HIF/VHL/VEGF and mitochondrial signalling pathways as potential targets for redox therapy.

Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases

“…Both studies showed that the treatment with antioxidants (NAC and curcumin) upregulates biogenesis [47,152,169]. Importantly, NAC and curcumin antioxidants have shown mitochondria protection by promoting bioenergetics preservation and maintaining redox homeostasis to avoid mtROS [16,94]. In 5/6 nephrectomy-induced CKD, the levels of PGC-1α decrease in a temporal course from two days after the nephrectomy, causing reductions in NRF1 and NRF2 [120].…”

Redox‐sensitive signaling pathways in renal cell carcinoma

“…21,28,29 The latter is because ROS at low levels act as secondary messengers. 20 H 2 O 2 and NO are considered the central redox signaling agents, 20,[30][31][32] promoting oxidative post-translational modifications (ox-PTMs) in proteins, changing their structure, localization, and function. 33,34 Ox-PTMs are principally produced in redoxsensitive amino acids such as cysteine (Cys) and methionine (Met) (Figure 1).…”

HPV and radiosensitivity of cervical cancer: a narrative review

“…Furthermore, hypoxia can potentially maintain or enhance the stem cell phenotype of cancer cells and contribute to the emergence of metastatic clones ( 14 ). E6 reduces antioxidant activity, and E7 inhibits glutathione transferase to reduce free radical scavenging, induces more reactive oxygen species and free radicals, and makes HPV+ tumors less hypoxic ( 15 ). It has been shown that radiotherapy combined with the hypoxic sensitizer nimorazole only improved the local control rate of HPV− head and neck squamous cell carcinoma, while HPV+ tumors did not benefit from it ( 16 ).…”