Ovarian cancer (OC) remains the most fatal gynecological malignancy worldwide. Approximately 90 % of OC cases are of epithelial origin, and despite cytotoxic chemotherapy, 70 % of patients experience relapses within three years. Due to the high mortality rate associated with recurrent OC, treatment continues to pose a significant clinical challenge [1]. Therefore, maintenance therapies using the anti-angiogenic agent bevacizumab and/or a poly (ADP-ribose) polymerase inhibitor (PARPi) have been widely adopted to reduce the risk of recurrence and have become the standard of care for patients with newly diagnosed advanced OC.
More recently, antibody-drug conjugates (ADCs) have emerged as promising targeted therapies for patients with recurrent OC. Among the various ADCs currently under development, trastuzumab deruxtecan (T-DXd), which targets human epidermal growth factor receptor 2 (HER2), and mirvetuximab soravtansine (MIRV), which targets folate receptor alpha (FRα), have demonstrated significant antitumor activity in HER2-expressing tumors and FRα-positive recurrent OC, respectively [2,3]. Both agents have been approved by the US Food and Drug Administration (FDA). Given their encouraging efficacy, ADCs represent a promising therapeutic option for recurrent and refractory OC. Several additional ADCs are being actively evaluated in clinical trials, indicating that the treatment landscape for this disease will continue to evolve.
As a result, there has been growing interest in the expression patterns and clinical significance of their molecular targets. HER2 is a representative example that serves as a target for T-DXd and functions as a transmembrane glycoprotein receptor that regulates diverse cellular processes by modulating multiple signaling pathways [4]. HER2 overexpression or amplification is correlated with aggressive tumor behavior and poor prognosis in several cancers, including OC [5,6]. The prevalence of HER2 positivity in OC varies widely across studies, ranging from 8 % to 76 %, depending on the detection method [e.g., immunohistochemistry (IHC) versus fluorescence in situ hybridization], scoring criteria, and study populations [[5], [6], [7]]. The gastric cancer scoring system [8] and the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) guidelines [9] have been widely adopted in clinical practice to assess HER2 expression status.
In this study, we aimed to evaluate the expression patterns of HER2 according to the histological type and clinically relevant biomarkers, including homologous recombination deficiency (HRD) status, mismatch repair (MMR) status, and programmed death-ligand 1 (PD-L1) expression, as well as their association with survival outcomes. Furthermore, we sought to investigate the overlap in overexpression of HER2 and FRα to support the development of optimal treatment strategies for OC.
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