Ovarian cancer, particularly high-grade serous ovarian cancer (HGSOC), remains one of the most difficult cancers to treat. Although chemotherapy is often effective initially, many patients relapse as the cancer develops resistance to commonly used drugs like cisplatin, limiting treatment options and leading to poor outcomes. MCW cancer scientists may have found a way to overcome this challenge—by targeting the Oncostatin M Receptor (OSMR), a protein that is highly expressed in some aggressive ovarian cancers and plays a crucial role in tumor progression. Findings of their new study, published in NPJ Precision Oncology, pave the way for the development of novel treatments to overcome chemotherapy resistance and reduce relapse in ovarian cancer, and potentially in other diseases.
“We discovered that OSMR helps ovarian cancer cells resist cisplatin by activating STAT3, a protein that drives cancer cell growth and spread. This activation triggers a signaling loop between OSMR and integrins, which promotes resistance to chemotherapy,” said co-author of the study Pradeep Chaluvally-Raghavan, PhD, Associate Professor, Obstetrics and Gynecology.
“By targeting OSMR, we aim to develop therapies that can overcome chemotherapy resistance, potentially improving long-term outcomes and reducing relapse rates in patients with ovarian cancer. Our findings offer a new therapeutic approach that could lead to more personalized and effective treatments, especially in cases where traditional therapies have failed,” he added.
In the study, the research team developed a new antibody that specifically targets and blocks the OSMR protein, halting the signals that promote cancer growth. The antibody also aids in breaking down the protein within cancer cells. Currently, there are no treatments approved by the U.S. Food and Drug Administration that target OSMR, leaving a gap in options for patients with OSMR-driven cancers. By focusing on this receptor, Dr. Chaluvally-Raghavan and the team aim not only to stop cancer from growing and spreading but also to enhance the body’s immune response against it, offering a new approach to treatment.
But the implications of their discovery extend far beyond ovarian cancer. OSMR is also found in other aggressive diseases, such as glioblastoma and pancreatic cancer, where its presence is linked to poor patient outcomes. “Our research could benefit not only patients with ovarian cancer but also those with other cancers driven by OSMR. This could lead to new treatments for multiple cancer types, improving survival rates and the quality of life for many patients,” explained Dr. Chaluvally-Raghavan.
The MCW Department of Obstetrics and Gynecology is at the forefront of cutting-edge gynecological cancer research, fueled by a uniquely collaborative environment that brings together gynecologic oncologists and basic science researchers. Dr. Chaluvally-Raghavan explained that this synergy allows the team to explore the underlying mechanisms of these cancers while developing novel therapies for clinical trials. “We are actively involved in developing monoclonal antibodies and small molecule inhibitors that could be used for treating gynecological cancers,” he said.
Looking ahead, Dr. Chaluvally-Raghavan and his team will assess the safety and effectiveness of their anti-OSMR antibody, with the goal of advancing it to clinical trials. They are also exploring ways to boost the immune system’s response by developing bi-specific antibodies that can recruit immune cells to attack cancer. “These efforts will expand the therapeutic impact of our work and bring us closer to more effective and innovative treatments for gynecological and other cancers that express OSMR,” he said.
Read the full study in NPJ Precision Oncology.