Impact of endosomal recycling inhibitors on drug resistant and immune tolerant breast cancers

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dc.check.date2025-12-31
dc.contributor.advisorLindsay, Andrew
dc.contributor.authorChembukavu, Suraj Narayananen
dc.date.accessioned2024-09-24T11:56:10Z
dc.date.available2024-09-24T11:56:10Z
dc.date.issued2024
dc.date.submitted2024
dc.description.abstractBreast cancer (BC) is the most common and frequent of all the cancers, accounting for about 25% of all the cases of cancer detected in women annually. There are a number of approved drugs on the market that have been developed or repurposed for the treatment of BC. However, a recurrent problem faced in the clinic is the emergence of drug resistance, which can be intrinsic or acquired. Prolonged periods of chemotherapeutics and targeted therapy have resulted in the development of acquired resistance through a number of different adaptations. This project focuses on resistance developed by various sub-types of breast cancer cells through drug-therapy-induced senescence. Previous studies have reported the cytoprotective nature of this cell cycle arrest phenomenon upon prolonged exposure to targeted- and chemotherapeutics. This study investigates specific molecular mechanisms governing therapy-induced senescence, the impact it has on the membrane trafficking of iron transporters, and the potential repurposing of endosomal recycling inhibitors (ERIs) to target these drug-tolerant cells. Additionally, we examined the effects of ERIs on the total protein and surface levels of immune checkpoint proteins. This was done by targeting the recycling of the glycoprotein PDL1, which is expressed on the surface of some tumour cells and binds to its cognate receptors on the surface of T cells. PDL1-PD1 binding leads to T cell inactivation. A number of ERIs were used to determine their impact on the levels of PDL1.
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationChembukavu, S. N. 2024. Impact of endosomal recycling inhibitors on drug resistant and immune tolerant breast cancers. MRes Thesis, University College Cork.
dc.identifier.endpage104
dc.identifier.urihttps://hdl.handle.net/10468/16431
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2024, Suraj Narayanan Chembukavu.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectBreast cancer
dc.subjectDrug resistance
dc.subjectTherapy-induced senescence
dc.subjectDoxorubicin
dc.subjectLapatinib
dc.subjectPrimaquine
dc.subjectMonensin
dc.subjectEndosomal recycling pathway
dc.subjectIron transporters
dc.subjectTransferrin receptor
dc.subjectFerritin
dc.subjectSenolytics
dc.titleImpact of endosomal recycling inhibitors on drug resistant and immune tolerant breast cancers
dc.typeMasters thesis (Research)en
dc.type.qualificationlevelMastersen
dc.type.qualificationnameMRes - Master of Researchen
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