头颈部鳞状细胞癌治疗中的分子靶向疗法

Molecular-targeted therapies in the treatment of squamous cell carcinomas of the head and neck.

作者信息

Le Tourneau Christophe, Siu Lillian L

机构信息

Department of Medical Oncology, Princess Margaret Hospital, Toronto, Canada.

出版信息

Curr Opin Oncol. 2008 May;20(3):256-63. doi: 10.1097/CCO.0b013e3282f9b575.

Abstract

PURPOSE OF REVIEW

The present study reviews recent developments of molecular-targeted therapies in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma. It also highlights ongoing research regarding predictive markers of sensitivity or resistance to anti-epidermal growth factor receptor agents and discusses some promising novel targets in head and neck squamous cell carcinoma, as well as clinical trial design challenges.

RECENT FINDINGS

Phase III randomized studies have brought the proof that cetuximab, an anti-epidermal growth factor receptor agent, is able to improve survival, either in combination with radiation therapy or in first-line treatment for recurrent and/or metastatic head and neck squamous cell carcinoma. In addition, promising results have been obtained with antiangiogenic therapies in phase II trials. Some clinical and molecular markers of resistance to anti-epidermal growth factor receptor agents have been identified, but they have not yet been validated for clinical practice. Other interesting targets, such as insulin-like growth factor 1R or the PI3K/AKT/mTOR pathway, have been shown in vitro to play key roles in head and neck squamous cell carcinoma, and their inhibition warrants further evaluations.

SUMMARY

Proof of the concept that molecular-targeted therapy is a valid therapeutic approach for head and neck squamous cell carcinoma has emerged with anti-epidermal growth factor receptor agents. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains the main challenge in the optimal selection of patients most likely to benefit from them.

摘要

综述目的

本研究回顾了分子靶向治疗在复发性和/或转移性头颈部鳞状细胞癌治疗中的最新进展。还重点介绍了关于抗表皮生长因子受体药物敏感性或耐药性预测标志物的正在进行的研究,并讨论了头颈部鳞状细胞癌中一些有前景的新靶点以及临床试验设计挑战。

最新发现

III期随机研究已证实,抗表皮生长因子受体药物西妥昔单抗与放射治疗联合应用或用于复发性和/或转移性头颈部鳞状细胞癌的一线治疗时,能够提高生存率。此外,抗血管生成疗法在II期试验中也取得了有前景的结果。已确定了一些抗表皮生长因子受体药物耐药的临床和分子标志物,但尚未在临床实践中得到验证。其他有趣的靶点,如胰岛素样生长因子1R或PI3K/AKT/mTOR通路,已在体外显示在头颈部鳞状细胞癌中起关键作用,对其抑制作用值得进一步评估。

总结

抗表皮生长因子受体药物已证明分子靶向治疗是头颈部鳞状细胞癌的一种有效治疗方法。然而,确定这些治疗的耐药或敏感预测生物标志物仍然是最有可能从治疗中获益的患者最佳选择的主要挑战。

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