Inhibition of the endosomal recycling pathway to overcome resistance to cancer therapies

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dc.availability.bitstreamcontrolled
dc.contributor.advisorLindsay, Andrewen
dc.contributor.authorFletcher, Kelsey
dc.date.accessioned2023-01-18T11:29:06Z
dc.date.available2023-01-18T11:29:06Z
dc.date.issued2022
dc.date.submitted2022
dc.description.abstractCancer is a major public health threat with incidence and mortality rates continuing to rise every year. Breast and prostate cancer are the most diagnosed cancers in women and men, respectively. Both cancers account for roughly 30% of all cancers diagnosed in each sex. Despite the continuous development of new therapies, drug resistance is a growing problem and is a major cause of cancer treatment failure, accounting for many cancer recurrences and deaths. Therefore, new drugs and treatment regimens are urgently required to overcome this resistance. Recent findings from our own lab and others have found that inhibition of the endosomal recycling pathway may be a promising strategy to downregulate clinically relevant cell surface proteins and to overcome drug resistance. This thesis focuses on two clinically relevant hormone receptors that are strongly linked to the development and progression of breast and prostate cancer linked to disease development and progression, the estrogen receptor alpha and the androgen receptor. The aim of this project was to confirm data obtained from a reverse-phase protein array (RPPA) study performed by our lab that found that the endosomal recycling inhibitor primaquine downregulates ER-α and AR expression. We used Western blot, quantitative RT-PCR, and immunofluorescence microscopy to confirm the RPPA results. We found that another endosomal recycling inhibitor, monensin, also potently downregulates these hormone receptors and that both inhibitors synergise with tamoxifen and enzalutamide, standard-of-care therapies for breast and prostate cancer. Keywords Cancer, prostate, breast, androgen receptor, estrogen receptor, endosomal recycling pathway, primaquine, monensin, drug resistance, tamoxifen, lapatinib, enzalutamide, synergy.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationFletcher, K. 2022. Inhibition of the endosomal recycling pathway to overcome resistance to cancer therapies. MSc Thesis, University College Cork.en
dc.identifier.endpage81en
dc.identifier.urihttps://hdl.handle.net/10468/14092
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2022, Kelsey Fletcher.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectCanceren
dc.subjectProstateen
dc.subjectBreasten
dc.subjectAndrogen receptoren
dc.subjectEstrogen receptoren
dc.subjectEndosomal recycling pathwayen
dc.subjectPrimaquineen
dc.subjectMonensinen
dc.subjectDrug resistanceen
dc.subjectTamoxifenen
dc.subjectLapatiniben
dc.subjectEnzalutamideen
dc.subjectSynergyen
dc.titleInhibition of the endosomal recycling pathway to overcome resistance to cancer therapiesen
dc.typeMasters thesis (Research)en
dc.type.qualificationlevelMastersen
dc.type.qualificationnameMRes - Master of Researchen
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