Endometrial cancer continues to represent a critical threat, being the leading cause of death among gynecologic cancers with an estimated 68,000 new cases diagnosed annually in the United States. The increasing incidence and mortality rates highlight the urgent need for new treatments to combat endometrial cancer effectively. Recent progress in treatment offers new hope, especially through innovative approaches at research centers like Dana-Farber Cancer Institute. We review the current state and advancements in the treatment and research of endometrial cancer reported by the Dana-Farber Cancer Institute.

Dana-Farber’s research efforts focus on four therapeutic areas:

• hormonal therapy,
• immunotherapy,
• antibody-drug conjugates, and
• targeting replication stress.

Each area represents a promising frontier for improving patient outcomes, especially for those with advanced or treatment-resistant endometrial cancer.

Hormonal Therapy

Traditionally used in breast and ovarian cancers, hormonal therapy is gaining traction in endometrial cancer. A Dana-Farber-led trial found that combining letrozole, an estrogen-lowering drug, with abemaciclib, a cancer cell division blocker, benefited 30% of participants, halting or shrinking tumors for nine months on average. These findings encouraged further trials to explore this combination as a potential standard therapy, especially for patients with endometrial cancer subtypes that typically resist immunotherapy.

Immunotherapy

Recent FDA approvals have highlighted immunotherapy’s growing role. Drugs like pembrolizumab, paired with chemotherapy, are now available for advanced endometrial cancer, marking a significant breakthrough. Trials led by Dana-Farber are further exploring combinations like avelumab and axitinib or talazoparib for patients with mismatch repair-proficient (MMRP) tumors, showing promise for those who typically do not respond to other treatments.

Antibody-Drug Conjugates (ADCs)

ADCs represent a novel strategy, attaching chemotherapy agents directly to tumor-seeking antibodies, sparing healthy cells. Ongoing trials at Dana-Farber are investigating the effects of ADCs such as trastuzumab deruxtecan and disitamab vedotin for HER2-positive tumors, with early results showing potential for reducing aggressive tumors.

Replication Stress

Leveraging a unique weakness in cancer cells, Dana-Farber researchers are studying replication stress—an interruption in DNA copying that impairs cell division. By blocking stress recovery mechanisms, they aim to push cancer cells to self-destruct. Funded by a major NCI grant, projects are in early stages but hold promise for long-term therapeutic development. Researchers are utilizing advanced lab models like organoids and xenografts to observe drug effects on tumor cells in real time, enhancing understanding of treatment response dynamics.

A Shift towards Personalized and Targeted Therapies

Dana-Farber’s comprehensive approach to endometrial cancer is bringing new hope to a field with limited treatment options. Researchers focus on treatments tailored to patients’ unique cancer subtypes, which could redefine standards of care. Targeted therapies, like antibody-drug conjugates, deliver precision strikes on cancer cells with fewer side effects. Immunotherapies boost the immune system’s natural ability to fight advanced cancers. Hormonal therapies now show effectiveness in cases that resist standard treatments. And research into replication stress is revealing new strategies to destroy cancer cells by exploiting their vulnerabilities. Together, these advances show Dana-Farber’s dedication to improving survival and quality of life for all patients facing endometrial cancer.