MCW Cancer Scientists Make a Breakthrough in Treating Aggressive Uterine Cancer

Patient and doctorUterine leiomyosarcoma (ULMS) is an aggressive, often hard-to-treat type of uterine cancer. Even when it’s detected early, ULMS is notorious for having poor outcomes and a high chance of recurrence after standard treatments. The results of a new MCW study provide hope for patients with this deadly disease, revealing that a novel combination of drugs, selinexor and eribulin, may be effective for treating ULMS and help to save more lives. The preclinical study, published in Experimental Hematology & Oncology, is the first ever to show the anti-cancer therapeutic potential of using these drugs in ULMS.

We discovered that selinexor, when combined with DNA damage-inducing chemotherapies like eribulin, showed synergistic effects and helped to potentiate the DNA damage-based therapies. DNA damage disrupts the integrity of cancer cell DNA, ultimately leading to cell death. The sequential combination of DNA damage agents followed by selinexor increased cancer cell death and reduced tumor size,” said study co-author Sunila Pradeep, PhD, associate professor of Obstetrics & Gynecology.

“Selinexor with eribulin was found to alter the expression of important transcription factors, leading to downstream changes within the tumor transcriptome. This combination demonstrated greater effectiveness than individual therapies and holds a mechanistic rationale as a novel anti-cancer strategy,” she added.

Compared to other types of uterine cancer, ULMS starts in the smooth muscle cells of the uterus and is more likely to spread to other parts of the body. The 5-year survival rate is also lower, ranging from 40% to 60%. Dr. Pradeep explained that currently, the most effective therapies for patients with recurring and advanced disease are associated with toxicity. Selinexor, a new selective inhibitor of nuclear export (SINE), may provide safer, more effective treatment by inhibiting a specific protein called exportin 1 (XPO1), which plays a crucial role in regulating the movement of proteins in and out of the cell’s nucleus.

“The drug reversibly binds to XPO1, thereby reactivating tumor suppressor proteins and downregulating the expression of oncogenes and DNA damage repair proteins,” said Dr. Pradeep.

So far, selinexor has been FDA-approved for treatment of multiple myeloma and diffuse large B cell lymphoma, but not for any solid tumors. Study co-author John Charlson, MD, associate professor of Medical Oncology, said the research team is working to develop a new clinical trial that will further test the novel drug combination in patients across Wisconsin.

“The rare nature of ULMS has resulted in few studies that are aimed at understanding its treatment. Our team is proud of this step forward in finding a cure, and for the positive impact it could bring to patients and families in our community,” said Dr. Charlson.

Read the full study in Experimental Hematology & Oncology.