Innovative Drug and Prodrug Candidates in Cancer Treatment Targeting TP53 Mutations: Challenge and Hope

The TP53 gene encodes the tumor suppressor protein 53, which is critical for maintaining genomic stability and preventing tumorigenesis. Mutations in TP53, particularly missense mutations, have a substantial impact on cancer progression because they give gain-of-function features that enhance proliferation, metastasis, and treatment resistance. This review examines the mechanisms underlying p53 mutations, including their interactions with critical regulatory circuits, and assesses novel medication and prodrug options targeting TP53 mutations in various malignancies. Small-molecule correctors, statins, Hsp90 inhibitors, and new drugs like Eprenetapopt and COTI-2 are among the therapeutic options proposed. The mechanisms of action and potential efficacy in treating leukemia, lung, breast, and ovarian malignancies are investigated. Emerging techniques for restoring wild-type p53 functionality or degrading mutant p53 demonstrate the therapeutic potential of these approaches. Challenges such as medication resistance, side effects, and the chemical complexity of p53 pathways are also addressed, emphasizing the importance of ongoing research. This review contributes to our understanding of TP53-targeted cancer medicines, offering hope for more innovative treatments with improved outcomes.

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Publication Details

Journal
Drug Development Research
Published
2026-02-10
DOI
https://doi.org/10.1002/ddr.70246
Primary Topic
Cancer-related Molecular Pathways
Type
article
Field-Weighted Citation Impact
0.00
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Innovative Drug and Prodrug Candidates in Cancer Treatment Targeting TP53 Mutations: Challenge and Hope

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Innovative Drug and Prodrug Candidates in Cancer Treatment Targeting TP53 Mutations: Challenge and Hope

Mai Elaarag, Hiba Bawadi, Ahmad R. Al‐Qudimat, Mazhar Salim Al Zoubi, Mona A. Sawali, Abdelali Agouni, Ayman A. Zarour, Zainab E. Fares, k. R. AlRumaihi, Khalil Garada, Mohanad Shkoor, Raed M. Al‐Zoubi, Sally R. Al‐Zoubi, Abbas Khan, Zain Z. Zakaria
article en

Abstract

The TP53 gene encodes the tumor suppressor protein 53, which is critical for maintaining genomic stability and preventing tumorigenesis. Mutations in TP53, particularly missense mutations, have a substantial impact on cancer progression because they give gain-of-function features that enhance proliferation, metastasis, and treatment resistance. This review examines the mechanisms underlying p53 mutations, including their interactions with critical regulatory circuits, and assesses novel medication and prodrug options targeting TP53 mutations in various malignancies. Small-molecule correctors, statins, Hsp90 inhibitors, and new drugs like Eprenetapopt and COTI-2 are among the therapeutic options proposed. The mechanisms of action and potential efficacy in treating leukemia, lung, breast, and ovarian malignancies are investigated. Emerging techniques for restoring wild-type p53 functionality or degrading mutant p53 demonstrate the therapeutic potential of these approaches. Challenges such as medication resistance, side effects, and the chemical complexity of p53 pathways are also addressed, emphasizing the importance of ongoing research. This review contributes to our understanding of TP53-targeted cancer medicines, offering hope for more innovative treatments with improved outcomes.

Drug Development ResearchVol. 87(2)
University of Debrecen (HU), Jordan University of Science and Technology (JO), Hamad Medical Corporation (QA), Qatar University (QA), Yarmouk University (JO)
Good health and well-being
Openalex Percentile: Top 60%
Cancer-related Molecular Pathways
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