"Adavosertib demonstrated remarkable activity as a single agent in this group of patients," says the study's lead author, Joyce Liu, MD, MPH, of Dana-Farber. "It's especially encouraging in a disease such as USC, for which current treatments are of limited effectiveness."
The preliminary results come from the phase I clinical trial of the drug, adavosertib, designed to demonstrate safety and determine optimal dose. In the trial 34 patients, all of whom had been previously treated with chemotherapy, took adavosertib orally on a set schedule.
After a follow up of nearly 4 months, 10 of the 34 patients saw their tumors shrink, showing the drug does affect the cancer, which is called a response rate. It is too early to know whether the drug’s effect will be prolonged, which would make it an effective treatment. Response rate just shows it might be effective.
Uterine serous carcinoma (USC), which accounts for about 10 percent of uterine cancers but up to 40 percent of deaths from the disease, is marked by a mutation in TP53, a key gene that plays a critical role in ensuring cell division proceeds accurately. If there is something wrong in the cell’s DNA, TP53 shuts down the cell division mechanism. When mutated or abnormal, TP53 fails and cell division proceeds unhindered, resulting in cancerous tumors.
In a fighting-fire-with-fire strategy, adavosertib targets a protein called WEE1 that helps TP53 regulate cell division. The goal is to suppress WEE1 so that tumor cells could be so overburdened with damaged DNA that the cell dies.
The researchers also reported that some of the patients have shown a durable response beyond a year following treatment, providing more hope that adavosertib may be a useful treatment. The most common side effects were anemia, diarrhea, nausea, and fatigue.
Source: Dana Farber press release
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