Cruz-Gregorio Alfredo, Martínez-Ramírez Imelda, Pedraza-Chaverri José, Lizano Marcela
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, San Fernando No. 22, Col. Sección XVI, Tlalpan, Ciudad de México 14080, México.
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México 04510, México.
Cancers (Basel). 2019 Feb 5;11(2):182. doi: 10.3390/cancers11020182.
Head and neck cancer (HNC) is the sixth cause of cancer-related death worldwide. Head and neck squamous cells carcinoma (HNSCC) is the most frequent subtype of HNC. The development of HNSCC is associated to alcohol consumption, smoking or infection by high-risk human Papillomavirus (HR-HPV). Although the incidence of cancers associated with alcohol and tobacco has diminished, HNSCC associated with HR-HPV has significantly increased in recent years. However, HPV-positive HNSCC responds well to treatment, which includes surgery followed by radiation or chemoradiation therapy. Radiation therapy (RT) is based on ionizing radiation (IR) changing cell physiology. IR can directly interact with deoxyribonucleic acid (DNA) or produce reactive oxygen and nitrogen species (RONS), provoking DNA damage. When DNA damage is not repaired, programmed cell death (apoptosis and/or autophagy) is induced. However, cancer cells can acquire resistance to IR avoiding cell death, where reprogramming of energy metabolism has a critical role and is intimately connected with hypoxia, mitochondrial physiology, oxidative stress (OS) and autophagy. This review is focused on the reprogramming of energy metabolism in response to RT in HPV-positive and HPV-negative HNSCC, showing their differences in cellular metabolism management and the probable direction of treatments for each subtype of HNSCC.
头颈癌（HNC）是全球第六大致癌相关死亡原因。头颈部鳞状细胞癌（HNSCC）是HNC最常见的亚型。HNSCC的发生与饮酒、吸烟或高危人乳头瘤病毒（HR-HPV）感染有关。尽管与酒精和烟草相关的癌症发病率有所下降，但近年来与HR-HPV相关的HNSCC显著增加。然而，HPV阳性的HNSCC对治疗反应良好，治疗包括手术，随后进行放疗或放化疗。放射治疗（RT）基于电离辐射（IR）改变细胞生理。IR可直接与脱氧核糖核酸（DNA）相互作用或产生活性氧和氮物种（RONS），引发DNA损伤。当DNA损伤未得到修复时，会诱导程序性细胞死亡（凋亡和/或自噬）。然而，癌细胞可获得对IR的抗性以避免细胞死亡，其中能量代谢重编程起着关键作用，并且与缺氧、线粒体生理、氧化应激（OS）和自噬密切相关。本综述聚焦于HPV阳性和HPV阴性HNSCC中能量代谢对RT的重编程，展示它们在细胞代谢管理方面的差异以及HNSCC各亚型可能的治疗方向。
