Theranostic implications of Nectin-4 oncoprotein in gynecologic cancers: A review

Gynecologic cancers, in order of prevalence, include uterine, ovarian, cervical, vaginal, and vulvar cancers. In 2024, there will be more than 116,000 new cases of gynecologic cancers and 33,800 disease-related deaths. Therefore, a concerted effort has been made to better understand the underlying pathophysiological processes and identify novel theranostic approaches.

Comprehensively examine the current peer-reviewed literature surrounding Nectin-4 and its implication in the identification and treatment of gynecologic cancers.

PubMed and Google search with relevant keywords for articles published in the last 15 years.

Nectin-4 as a cell adhesion molecule (CAM) promotes cell growth through intra-tumoral angiogenesis, strengthens cell-cell bonds, and creates a tight spheroid structure, which is more chemotherapy resistant. In high-grade serous ovarian cancer (HGSOC), Nectin-4 is strongly associated with the presence of peritoneal metastases and worse prognoses. When compared to CA-125, a common tumor marker for ovarian cancer, Nectin-4 showed higher specificity and sensitivity for predictive value of tumorigenesis. Regarding cervical cancer, inhibition of Nectin-4 by nanoformulated Quinacrine inhibits both cancer stem cell proliferation and DNA damage. Nectin-4 as a tumor marker can discriminate endometrial cancer from healthy adjacent tissue with a specificity of 95.4 % and sensitivity of 82.81 %. Lastly, there is scarce evidence of Nectin-4 and fallopian tube, vaginal, or vulvar cancer but given ovarian cancer cells may originate from the fallopian tube, there is plausibility of using Nectin-4 to detect fallopian and/or ovarian cancer earlier.

Overall, Nectin-4 as a promoter of cancer cell growth and metastasis supports the emphasis in current peer-reviewed literature as an effective theranostic biomarker.