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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.