dc.contributor.advisor | McMillan, Nigel | |
dc.contributor.author | Tayyar, Yaman A | |
dc.date.accessioned | 2021-10-01T04:33:45Z | |
dc.date.available | 2021-10-01T04:33:45Z | |
dc.date.issued | 2021-09-15 | |
dc.identifier.doi | 10.25904/1912/4357 | |
dc.identifier.uri | http://hdl.handle.net/10072/408504 | |
dc.description.abstract | Human papillomavirus (HPV) and its oncogenes (E6 and E7) are responsible for 5% of the entire burden of cancer and more than 99% of all cervical cancer cases. Although protection against infection was made possible with the introduction of vaccines, several challenges related to their rollout, subtype coverage, and their lack of therapeutical potential mean that little will change for several decades. Accordingly, the currently available armamentarium for the treatment of cervical cancer has not led to improvement in the therapeutic outcomes since the 1970s. In this context, the discovery of the clustered regularly interspaced short palindromic repeats (CRISPR) and the advancements in our understanding of the molecular mechanisms in the carcinogenic process have kept the doors wide open for developing potent and selective treatments for these cancers. In this thesis, we developed and utilised a messenger RNA (mRNA) modality of the highly specific AsCPF1 nuclease and optimised its topical delivery for the treatment of cervical cancer using PEGylated lipoplex-entrapped alginate scaffold (PLAS) platform. In addition, we described a potent molecular-based combination therapy for systemic administration to inhibit Aurora Kinase A (AURKA) and Phosphatidylinositol 3-kinase (PI3K) using Alisertib and Alpelisib, respectively, and we showed the sensitivity of cervical cancer to this synergistic combination. Overall, this research demonstrates the viability of improving the therapeutic outcomes for HPV-driven cancers in general and cervical cancers if careful consideration of the driving molecular mechanisms was undertaken. We showed the feasibility of safely delivering CRISPR systems using PEGylated lipoplex-entrapped alginate scaffold for the topical targeting of cervical cancer, providing new insights into the translation of CRISPR into humans, and we developed a potent molecular-based combination therapy for improving the outcomes of the treatment. | en_US |
dc.language | English | |
dc.language.iso | en | |
dc.publisher | Griffith University | |
dc.publisher.place | Brisbane | |
dc.subject.keywords | Human papillomavirus | en_US |
dc.subject.keywords | HPV | en_US |
dc.subject.keywords | Cervical cancer | en_US |
dc.subject.keywords | Treatment | en_US |
dc.title | Development of Novel Therapies for Human Papilloma Virus Driven Cancers | en_US |
dc.type | Griffith thesis | en_US |
gro.faculty | Griffith Health | en_US |
gro.rights.copyright | The author owns the copyright in this thesis, unless stated otherwise. | |
gro.hasfulltext | Full Text | |
dc.contributor.otheradvisor | Idris, Adi | |
dc.contributor.otheradvisor | Parekh, Harendra | |
gro.identifier.gurtID | 000000024173 | en_US |
gro.thesis.degreelevel | Thesis (PhD Doctorate) | en_US |
gro.thesis.degreeprogram | Doctor of Philosophy (PhD) | en_US |
gro.department | School of Pharmacy & Med Sci | en_US |
gro.griffith.author | Tayyar, Yaman A | |