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针对复发性或晚期宫颈癌治疗的泛 HER 靶向方法:机制、最新进展和临床前景。

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

机构信息

Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4123-4131. doi: 10.26355/eurrev_202004_20992.

Abstract

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.

摘要

目的

表皮生长因子受体(EGFR)蛋白的过度表达以及基因扩增与复发性宫颈癌及其晚期密切相关,并且直接影响疾病的预后。以下是 HER 家族的成员:(i)EGFR/HER1;(ii)HER2;(iii)HER3;和(iv)HER4。图 1 显示了其信号通路。成员之间的协同作用促进肿瘤细胞的免疫逃逸,从而导致对 HER 抑制剂的耐受性。广泛的 HER 抑制剂,即 pan-HER 抑制剂,可以不可逆地抑制细胞膜上的 HER 受体与其配体结合,从而阻断下游信号转导级联反应,抑制肿瘤生长、黏附、侵袭、分化和转移。因此,pan-HER 抑制剂可能是治疗复发性或晚期宫颈癌的一个研究领域。

材料和方法

通过回顾 HER 家族受体及其分子机制,我们可以得出结论,pan-HER 抑制剂确实对复发性或晚期宫颈癌患者的治疗有积极影响。

结果

本文综述了 HER 家族受体的分子机制、HER 抑制剂的最新进展以及 pan-HER 抑制剂在治疗复发性或晚期宫颈癌中的潜在临床影响。

结论

pan-HER 抑制剂已被证明可改善复发性或晚期宫颈癌患者的预后。临床前研究结果显示出良好的前景,并且有可能改善复发性或晚期宫颈癌患者的治疗效果。pan-HER 抑制剂在临床和临床前研究中与化疗联合使用时也显示出协同作用。然而,需要对 pan-HER 抑制剂与放疗和其他靶向抑制剂的联合使用进行长期研究。这些抑制剂是否比单一 HER 靶向药物更有效地穿过血脑屏障,这可能是未来研究的一个关注点。这一想法将在临床宫颈癌试验中进行探索。

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