WEE1 inhibitor: clinical development

Anthony Kong, Hisham Mehanna

Research output: Contribution to journalArticlepeer-review

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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.

Summary
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-tumour efficacy with a good safety profile compared to monotherapy and/or standard treatment.

Original languageEnglish
Article number107
Number of pages8
JournalCurrent oncology reports
Volume23
Issue number9
DOIs
Publication statusPublished - 16 Jul 2021

Keywords

  • Adavosertib
  • TP53 mutation
  • WEE 1 inihibitor
  • biomarker
  • clinical trials

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