A pan-HER-targeted approach for recurrent or late-stage cervical cancer therapy: mechanisms, recent advances, and clinical prospects

Y. Liu, Q. An, X. Zhao

Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China. Xia-Zhao@126.com

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• Oncology

OBJECTIVE: Over-expression of the epidermal growth factor receptor (EGFR) protein, along with gene amplification, is closely associated with recurrent cervical cancer and the disease’s advanced stages. Additionally, it can have a direct impact on the disease’s prognosis. The following are the members of the HER family: (i) EGFR/HER1; (ii) HER2; (iii) HER3; and (iv) HER4. Figure 1 shows its signalling pathway. The synergy between the members facilitates immune escape by tumour cells, which can lead to tolerance to HER inhibitors. A broad HER inhibitor, a pan-HER inhibitor, can irreversibly inhibit a cell membrane’s HER receptors to their ligands, thereby blocking downstream signal-transduction cascades, inhibiting tumour growth, adhesion, invasion, differentiation, and metastasis. As such, pan-HER inhibitors may be an area of interest in treating recurrent or late-stage cervical cancer.
MATERIALS AND METHODS: Through a review of HER-family receptors and their molecular mechanism, we can conclude that pan-HER inhibitors do indeed have a positive impact on therapy for recurrent or late-stage cervical cancer patients.
RESULTS: This paper reviews the molecular mechanism that underlies receptors within the HER family, current developments in HER inhibitors, and the potential clinical impacts of pan-HER inhibitors in treating recurrent or late-stage cervical cancer.
CONCLUSIONS: Pan-HER inhibitors have been shown to improve prognoses for recurrent or late-stage cervical cancer patients. Preclinical studies show promising results, as well as the potential to improve results for recurrent or late-stage cervical cancer patients. Pan-HER inhibitors have also shown synergistic results in clinical and pre-clinical settings when combined with chemotherapy. However, long-term study is required regarding the combination of pan-HER inhibitors with radiotherapy and other targeted inhibitors. The question of whether or not these inhibitors have a more potent effect across the blood-brain barrier when compared to single HER-targeting agents may be an area of interest for future research. This idea will be explored in clinical cervical cancer trials.

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