A new study published in npj Precision Oncology suggests that a class of drugs called MDM2 inhibitors could make radiotherapy more effective for people with endometrial cancer (EC), the most common gynecological cancer.
EC rates are rising worldwide, yet treatment advancements have been limited. Radiotherapy is often used after surgery or for advanced disease, but not all patients respond equally well.
Researchers focused on TP53, a tumor-suppressing gene that helps radiation kill cancer cells. When there’s a mutation of this gene, tumors can become resistant to radiation, leading to poorer prognoses.
Learn more about endometrial cancer prognosis
The research tested whether blocking MDM2, a protein that breaks down TP53, could restore sensitivity to radiation. By using MDM2 inhibitors, researchers aimed to stabilize p53, the protein produced by TP53, and improve radiation’s effectiveness.
In lab experiments, combining MDM2 inhibitors with radiation killed significantly more cancer cells than either approach alone, especially when cells still had at least one functioning copy of TP53. The study authors described the effect as synergistic, meaning the treatments worked better together than the sum of their parts.
The researchers also tested the strategy in mice implanted with human endometrial tumors, and the experiment yielded similar results.
The findings suggest that TP53 status may determine which patients are most likely to benefit from this combined approach. Those with tumors that retain some TP53 function could see improved outcomes if MDM2 inhibitors are added to standard radiotherapy.
While the study was limited to cells and animal models, the researchers say it provides a strong rationale for clinical trials in people.
“Taken together, our data support established clinical trials in EC and advocate for genomics-driven clinical trials that incorporate biologics with radiotherapy in recurrent and early-stage EC,” they concluded.
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