The Impact of
Mutations on the Molecular Structure of the Cancer Biomarker X-linked Inhibitor
of apoptosis protein (XIAP) and drug binding ensuring personalized drug selection
Tepap Zemnou Cromwel
Res. J. Chem. Environ.; Vol. 30(1); 71-92;
doi: https://doi.org/10.25303/301rjce071092; (2026)
Abstract
The X-linked inhibitor of apoptosis protein (XIAP) inhibits caspases 3, 7 and 9,
blocking apoptosis and promoting cancer development. Malfunctions of XIAP due to
single nucleotide polymorphisms (SNPs) can cause X-linked lymphoproliferative syndrome
type 2, an immunodeficiency. While several drugs targeting XIAP are in development,
no in silico studies have evaluated the impact of SNPs on XIAP’s molecular function
and drug-binding affinity. This study uses computational methods to assess XIAP's
molecular expression and prognostic value in various cancers and the effects of
SNPs on XIAP’s interactions with four inhibitors. Our findings show that XIAP is
overexpressed in six cancers out of 33 examined in the GEPIA2 database. XIAP overexpression
was correlated with cancer stages only in pancreatic adenocarcinoma (PAAD) and was
linked to survival and prognosis in adrenocortical carcinoma (ACC), kidney renal
clear cell carcinoma (KIRC) and oropharyngeal squamous cell carcinoma (OPSCC).
The study also revealed that SNPs can alter XIAP's structure, influencing patient
responses to chemotherapy. Drugs with lower inhibitory capacity like GDC-0152 and
TL32711 may be more effective for treating patients with these mutations. These
findings emphasize the need for more research on XIAP genetic polymorphism to better
determine its prognostic significance across cancers and to enhance precision medicine.
