PI3K/Akt/mTOR signaling pathway on targeted therapies of head and neck squamous cell carcinoma

doi:10.3877/cma.j.issn.1674-1366.2019.05.001

Abstract

Abstract:

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause for cancer-related mortality worldwide. Personalized medicine of targeted drugs combined with classical radiotherapy and chemotherapy after surgery is expected to improve therapeutic efficacy and prolong survival rate of patients. It is known that increasing activation of PI3K/Akt/mTOR signaling pathway in HNSCC plays a central role to drive tumorigenesis and cancer metastasis. This article will explore the potential molecular mechanisms of individual differences in PI3K/Akt/mTOR signaling pathway applied in targeted therapy, the progress and current dilemmas of clinical trials, to provide a scheme for clinical treatment strategies to improve the life quality of the patients.

Key words: Head and neck neoplasms, Carcinoma, squamous cell, Molecular targeted therapy, PI3K/Akt/mTOR signaling pathway

Yihan Xing, Zhuoying Li, Baoshan Xu. PI3K/Akt/mTOR signaling pathway on targeted therapies of head and neck squamous cell carcinoma[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2019, 13(05): 257-264.

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References 56

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药物		试验编码	阶段	使用方法	受试群体
EGFR抑制剂		?	?	?	?
?	西妥昔单抗	NCT00468169	Ⅱ	分别联合5-氟尿嘧啶、羟基脲、放疗和顺铂、放疗	Ⅲ、Ⅳ期头颈部鳞状细胞癌
		NCT00409565	Ⅱ	联合贝伐单抗	复发和转移头颈部鳞状细胞癌
		NCT02110082	Ⅰb	联合乌鲁单抗(Urelumab)	晚期和转移头颈部鳞状细胞癌
?	帕尼单抗	NCT00500760	Ⅱ	联合顺铂	局部晚期头颈部鳞状细胞癌
		NCT03733210	Ⅰ	单药	头颈部鳞状细胞癌
		NCT02415881	Ⅰ	单药	头颈部鳞状细胞癌
?	厄洛替尼	NCT00570232	Ⅱ	单药	复发性头颈部鳞状细胞癌
		NCT00942734	Ⅱ	联合依维莫司	复发性头颈部鳞状细胞癌
		NCT00970502	Ⅰ/Ⅱ	联合塞来昔布	头颈部鳞状细胞癌
?	吉非替尼	NCT00519077	Ⅱ	单药	复发和转移头颈部鳞状细胞癌
?	阿法替尼	NCT02979977	Ⅱ	联合西妥昔单抗	局部晚期、复发和转移头颈部鳞状细胞癌
		NCT01824823	Ⅱ	单药	Ⅲ、Ⅳ期头颈部鳞状细胞癌
		NCT01345682	Ⅲ	单药	复发和转移头颈部鳞状细胞癌
?	拉帕提尼	NCT00387127	Ⅱ	联合顺铂、放疗	头颈部鳞状细胞癌
?	拉帕提尼	NCT00424255	Ⅲ	联合放化疗	Ⅱ、Ⅲ、Ⅳa期头颈部鳞状细胞癌
VEGFR抑制剂		?	?	?	?
?	贝伐珠单抗	NCT00409565	Ⅱ	联合西妥昔单抗	复发和转移头颈部鳞状细胞癌
		NCT00423930	Ⅱ	联合顺铂、放疗	Ⅲ、Ⅳ期头颈部鳞状细胞癌
		NCT00222729	Ⅱ	联合培美曲塞	复发和转移头颈部鳞状细胞癌
?	福林替尼	NCT00725764	Ⅱ	单药	复发和转移头颈部鳞状细胞癌
IGFR抑制剂		?	?	?	?
?	Cixutumumab	NCT00617734	Ⅱ	单药或联合西妥昔单抗	复发和转移头颈部鳞状细胞癌
FGFR抑制剂		?	?	?	?
?	Infigratinib	NCT02706691	Ⅱ	单药	存在FGFR1-3基因改变的头颈部鳞状细胞癌
?	Rogaratinib	NCT01976741	Ⅰ	单药	局部晚期和转移实体瘤
PDGFR抑制剂		?	?	?	?
?	伊马替尼	NCT00485485	Ⅱ	联合紫杉醇	复发和转移头颈部鳞状细胞癌
PI3K抑制剂		?	?	?	?
?	Alpelisib	NCT02537223	Ⅰ	联合顺铂、放化疗	局部晚期头颈部鳞状细胞癌
		NCT02145312	Ⅱ	单药	复发和转移头颈部鳞状细胞癌
		NCT02051751	Ⅰb	联合紫杉醇	复发和转移头颈部鳞状细胞癌
?	Buparlisib	NCT02113878	Ⅰb	联合顺铂、放化疗	Ⅲ、Ⅳ期头颈部鳞状细胞癌
?	Gedatolisib	NCT03065062	Ⅰ	联合哌柏西利(Palbociclib，PD-0332991)	晚期肺、胰腺、头颈部鳞状细胞瘤及其他实体瘤
Akt抑制剂		?	?	?	?
?	MK-2206	NCT01349933	Ⅱ	单药	Ⅳ期、复发鼻咽鳞状细胞癌
mTOR抑制剂		?	?	?	?
?	雷帕霉素	NCT01283334	Ⅰ/Ⅱb	联合卡铂、西妥昔单抗、依维莫司	复发和转移头颈部鳞状细胞癌
?	雷帕霉素	NCT00942734	Ⅱ	联合厄洛替尼	复发性头颈部鳞状细胞癌
?	坦西莫司	NCT01016769	Ⅰ/Ⅱ	联合紫杉醇、卡铂	复发和转移头颈部鳞状细胞癌
?	坦西莫司	NCT01256385	Ⅱ	联合西妥昔单抗	复发和转移头颈部鳞状细胞癌
?	依维莫司	NCT03578432	Ⅰ	单药	放化疗后局部晚期头颈部鳞状细胞癌
?	依维莫司	NCT00942734	Ⅱ	联合厄洛替尼	复发性头颈部鳞状细胞癌

药物		试验编码	阶段	使用方法	受试群体
EGFR抑制剂		?	?	?	?
?	西妥昔单抗	NCT00468169	Ⅱ	分别联合5-氟尿嘧啶、羟基脲、放疗和顺铂、放疗	Ⅲ、Ⅳ期头颈部鳞状细胞癌
		NCT00409565	Ⅱ	联合贝伐单抗	复发和转移头颈部鳞状细胞癌
		NCT02110082	Ⅰb	联合乌鲁单抗(Urelumab)	晚期和转移头颈部鳞状细胞癌
?	帕尼单抗	NCT00500760	Ⅱ	联合顺铂	局部晚期头颈部鳞状细胞癌
		NCT03733210	Ⅰ	单药	头颈部鳞状细胞癌
		NCT02415881	Ⅰ	单药	头颈部鳞状细胞癌
?	厄洛替尼	NCT00570232	Ⅱ	单药	复发性头颈部鳞状细胞癌
		NCT00942734	Ⅱ	联合依维莫司	复发性头颈部鳞状细胞癌
		NCT00970502	Ⅰ/Ⅱ	联合塞来昔布	头颈部鳞状细胞癌
?	吉非替尼	NCT00519077	Ⅱ	单药	复发和转移头颈部鳞状细胞癌
?	阿法替尼	NCT02979977	Ⅱ	联合西妥昔单抗	局部晚期、复发和转移头颈部鳞状细胞癌
		NCT01824823	Ⅱ	单药	Ⅲ、Ⅳ期头颈部鳞状细胞癌
		NCT01345682	Ⅲ	单药	复发和转移头颈部鳞状细胞癌
?	拉帕提尼	NCT00387127	Ⅱ	联合顺铂、放疗	头颈部鳞状细胞癌
?	拉帕提尼	NCT00424255	Ⅲ	联合放化疗	Ⅱ、Ⅲ、Ⅳa期头颈部鳞状细胞癌
VEGFR抑制剂		?	?	?	?
?	贝伐珠单抗	NCT00409565	Ⅱ	联合西妥昔单抗	复发和转移头颈部鳞状细胞癌
		NCT00423930	Ⅱ	联合顺铂、放疗	Ⅲ、Ⅳ期头颈部鳞状细胞癌
		NCT00222729	Ⅱ	联合培美曲塞	复发和转移头颈部鳞状细胞癌
?	福林替尼	NCT00725764	Ⅱ	单药	复发和转移头颈部鳞状细胞癌
IGFR抑制剂		?	?	?	?
?	Cixutumumab	NCT00617734	Ⅱ	单药或联合西妥昔单抗	复发和转移头颈部鳞状细胞癌
FGFR抑制剂		?	?	?	?
?	Infigratinib	NCT02706691	Ⅱ	单药	存在FGFR1-3基因改变的头颈部鳞状细胞癌
?	Rogaratinib	NCT01976741	Ⅰ	单药	局部晚期和转移实体瘤
PDGFR抑制剂		?	?	?	?
?	伊马替尼	NCT00485485	Ⅱ	联合紫杉醇	复发和转移头颈部鳞状细胞癌
PI3K抑制剂		?	?	?	?
?	Alpelisib	NCT02537223	Ⅰ	联合顺铂、放化疗	局部晚期头颈部鳞状细胞癌
		NCT02145312	Ⅱ	单药	复发和转移头颈部鳞状细胞癌
		NCT02051751	Ⅰb	联合紫杉醇	复发和转移头颈部鳞状细胞癌
?	Buparlisib	NCT02113878	Ⅰb	联合顺铂、放化疗	Ⅲ、Ⅳ期头颈部鳞状细胞癌
?	Gedatolisib	NCT03065062	Ⅰ	联合哌柏西利(Palbociclib，PD-0332991)	晚期肺、胰腺、头颈部鳞状细胞瘤及其他实体瘤
Akt抑制剂		?	?	?	?
?	MK-2206	NCT01349933	Ⅱ	单药	Ⅳ期、复发鼻咽鳞状细胞癌
mTOR抑制剂		?	?	?	?
?	雷帕霉素	NCT01283334	Ⅰ/Ⅱb	联合卡铂、西妥昔单抗、依维莫司	复发和转移头颈部鳞状细胞癌
?	雷帕霉素	NCT00942734	Ⅱ	联合厄洛替尼	复发性头颈部鳞状细胞癌
?	坦西莫司	NCT01016769	Ⅰ/Ⅱ	联合紫杉醇、卡铂	复发和转移头颈部鳞状细胞癌
?	坦西莫司	NCT01256385	Ⅱ	联合西妥昔单抗	复发和转移头颈部鳞状细胞癌
?	依维莫司	NCT03578432	Ⅰ	单药	放化疗后局部晚期头颈部鳞状细胞癌
?	依维莫司	NCT00942734	Ⅱ	联合厄洛替尼	复发性头颈部鳞状细胞癌

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