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oai:figshare.com:article/32805587 2026-10-01T16:14:51Z portal_1172 item_type_8 month_year_10_2026

Enhancing the neoadjuvant treatment of rectal cancer by targeting the Inhibitor of Apoptosis Proteins Timothy O'Brien (144854) PUREID: 681726649 Rectal cancer total neoadjuvant therapy apoptosis tolinapant Total neoadjuvant therapy (TNT) has emerged as a standard approach for locally advanced rectal cancer, combining (chemo)radiation and systemic chemotherapy prior to surgery. This strategy improves tumour downstaging, increasing the likelihood of non-operative management, and reduces local and distant recurrence. However, most patients still require major surgery, and approximately 25% ultimately relapse. Enhancing tumour cell death during TNT may improve these outcomes.<br><br>Inhibitor of Apoptosis Proteins (IAPs) are upregulated in rectal cancer and are associated with treatment resistance and poor prognosis. Additionally, intratumoral bacteria such as Fusobacterium nucleatum may contribute to IAP-mediated resistance. This thesis investigates whether pharmacological inhibition of IAPs using the Smac-mimetic tolinapant can enhance responses to TNT.<br><br><i>Thesis is embargoed until 31 July 2027.</i> 2026-10-01T16:14:51Z Text Thesis 10.17034/32805587.v1 https://figshare.com/articles/thesis/Enhancing_the_neoadjuvant_treatment_of_rectal_cancer_by_targeting_the_Inhibitor_of_Apoptosis_Proteins/32805587 All Rights Reserved Open Access after 2027-07-31