WEE1 Inhibitor: Clinical Development

Overview

Journal Curr Oncol Rep

Publisher Current Science

Specialty Oncology

Date 2021 Jul 16

PMID 34269904

Citations 32

Authors

Anthony Kong

Hisham Mehanna

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents.

Recent Findings: Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

Citing Articles

Cyclin E1 overexpression sensitizes ovarian cancer cells to WEE1 and PLK1 inhibition.

Xi Q, Kunita A, Ogawa M, Ka M, Tanimoto S, Tsuchimochi S Oncogene. 2025; .

PMID: 39994376 DOI: 10.1038/s41388-025-03312-4.

High WEE1 expression is independently linked to poor survival in multiple myeloma.

Simhal A, Firestone R, Oh J, Avutu V, Norton L, Hultcrantz M Blood Cancer J. 2025; 15(1):22.

PMID: 39979284 PMC: 11842801. DOI: 10.1038/s41408-025-01230-y.

[Next generation sequencing (NGS)-based molecular panel analysis for metastatic prostate cancer: how often can we detect druggable mutations? : NGS for metastatic adenocarcinoma of the prostate].

Steenbock O, Paffenholz P, Rieger C, Heidenreich J, Pfister D, von Brandenstein M Urologie. 2025; 64(3):256-268.

PMID: 39836208 PMC: 11893637. DOI: 10.1007/s00120-024-02493-2.

The RING Finger E3 Ligase RNF25 Protects DNA Replication Forks Independently of its Canonical Roles in Ubiquitin Signaling.

Chiou L, Jayaprakash D, Droby G, Zhang X, Yang Y, Mills C bioRxiv. 2025; .

PMID: 39829812 PMC: 11741350. DOI: 10.1101/2025.01.09.632184.

Targeting refractory diffuse large B cell lymphoma by CAR-WEE1 T-cells: In vitro evaluation.

Ahmed H, Moselhy S, Mohamad M, Soliman A, Hassan M, El-Khazragy N Ann Hematol. 2025; .

PMID: 39820427 DOI: 10.1007/s00277-024-06134-8.

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