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

Drug development research 2026 Vol.87(2) p. e70246

Al-Zoubi RM, Elaarag M, Zarour AA, Garada K, Al-Zoubi SR, Fares ZE, Al-Qudimat AR, Shkoor M, Khan A, Sawali MA, Bawadi H, Zakaria ZZ, Zoubi MA, Agouni A, Alrumaihi K

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The TP53 gene encodes the tumor suppressor protein 53, which is critical for maintaining genomic stability and preventing tumorigenesis.

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BibTeX ↓ RIS ↓
APA Al-Zoubi RM, Elaarag M, et al. (2026). Innovative Drug and Prodrug Candidates in Cancer Treatment Targeting TP53 Mutations: Challenge and Hope.. Drug development research, 87(2), e70246. https://doi.org/10.1002/ddr.70246
MLA Al-Zoubi RM, et al.. "Innovative Drug and Prodrug Candidates in Cancer Treatment Targeting TP53 Mutations: Challenge and Hope.." Drug development research, vol. 87, no. 2, 2026, pp. e70246.
PMID 41665206
DOI 10.1002/ddr.70246

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.

MeSH Terms

Humans; Prodrugs; Neoplasms; Tumor Suppressor Protein p53; Antineoplastic Agents; Animals; Mutation

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