Adavosertib in Uterine Cancer
by Dr. C.H. Weaver M.D. 5/17/21
A novel precision cancer medicine that subjects tumor cells to staggering levels of DNA damage resulted in nearly one-third of hard to treat uterine cancers to respond to treatment according to a recent publication by doctors a the Dana-Farber Cancer Institute. (2)
About Adavosertib (AZD1775)
Adavosertib is a small molecule “Wee1 inhibitor” of the tyrosine kinase WEE1 with potential cancer sensitizing activity that can make some cancer cells more vulnerable to anti-cancer therapy and enhance its cytotoxic effect.
Adavosertib has shown anticancer activity in pancreatic and other hard to treat cancers. (2) Doctors have now reported results of a small trial involving 35 patients with refractory uterine cancer all of whom had previously been treated with platinum-based chemotherapy. At a median follow-up of 5.9 months, 30% of evaluated patients experienced a response to treatment including one patient with a complete response. The median duration of response was 9.0 months, and 47% of patients remained without cancer progression 6 months from beginning treatment.
More than 90% of serous uterine cancers have a mutation or other abnormality in the TP53 gene, which plays a critical role in the checkpoint between the first phase of cell growth and the DNA-duplication phase. Without a working TP53 gene, cells can barrel into the DNA-duplication phase with extensive DNA damage on board. Adavosertib targets the WEE1 protein that helps regulate replication.
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Adavosertib was well tolerated and the most common side effects of the treatment were anemia, diarrhea, nausea, and fatigue
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References
- Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer
- [https://ascopubs.org/doi/abs/10.1200/JCO.20.03167](Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma)
