Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma.
Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma.
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DOI：
10.3390/cancers13061193
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发表时间：
2021-03-10
期刊：
影响因子：
5.2
通讯作者：
Kim HC
中科院分区：
文献类型：
--
作者：
Cho WJ;Kessel D;Rakowski J;Loughery B;Najy AJ;Pham T;Kim S;Kwon YT;Kato I;Kim HE;Kim HC
尽管多模态治疗策略取得了进展，但超过30%的晚期头颈部鳞状细胞癌（HNSCC）患者的疾病复发通常来自残留肿瘤。本研究的目的是了解晚期HNSCC放射治疗抵抗的分子基础，并确定一种基于机制的放射增敏剂。我们发现自噬细胞存活途径在治疗抗性HNSCC中上调。针对内质网（ER）/线粒体的光动力疗法（PDT）以自噬适配器p62依赖性方式诱导程序性细胞死亡，如凋亡和凋亡，从而促进放射毒性。尽管最近的进展，如放射化疗的治疗方式，晚期头颈部鳞状细胞癌（HNSCC），特别是非病毒HNSCC患者的长期预后仍然非常差，而生存的人乳头瘤病毒（HPV）相关的HNSCC患者放疗后大大提高。本研究的目的是为HPV阴性的HNSCC高危患者制定一种基于机制的治疗方案。为了实现我们的目标，我们研究了HPV阳性和阴性HNSCC细胞之间差异辐射敏感性的分子机制。在此，我们发现自噬与HPV阴性HNSCC的放射抗性相关，而凋亡与放射敏感的HPV阳性HNSCC相关。有趣的是，我们发现，光动力疗法（PDT）针对内质网（ER）/线粒体最初诱导paraptosis，然后凋亡。这导致HPV阴性HNSCC的辐射反应性大幅增加，而相同的PDT治疗对HPV阳性细胞的影响最小。在这里，我们提供的证据表明，自噬适配器p62介导的信号中继诱导细胞凋亡，促进电离辐射（XRT）诱导的细胞死亡HPV阴性HNSCC。这项工作提出，ER/ESTA靶向PDT可以作为一种放射增敏剂在固有的放射抗性HNSCC表现出增加的自噬通量。
Despite the advances in multimodality treatment strategies, more than 30% of patients with advanced head and neck squamous cell carcinoma (HNSCC) experience recurrence of the disease that is usually derived from the residual tumor. The goal of our study is to understand the molecular basis underlying radiotherapy resistance in advanced HNSCC and to identify a mechanism-based radiosensitizer. We found that the autophagic cell survival pathway is upregulated in therapy-resistant HNSCC. Photodynamic therapy (PDT) directed at the endoplasmic reticulum (ER)/mitochondria induces programmed cell death such as paraptosis and apoptosis in an autophagic adaptor p62-dependent manner, promoting radiotoxicity. Despite recent advances in therapeutic modalities such as radiochemotherapy, the long-term prognosis for patients with advanced head and neck squamous cell carcinoma (HNSCC), especially nonviral HNSCC, remains very poor, while survival of patients with human papillomavirus (HPV)-associated HNSCC is greatly improved after radiotherapy. The goal of this study is to develop a mechanism-based treatment protocol for high-risk patients with HPV-negative HNSCC. To achieve our goal, we have investigated molecular mechanisms underlying differential radiation sensitivity between HPV-positive and -negative HNSCC cells. Here, we found that autophagy is associated with radioresistance in HPV-negative HNSCC, whereas apoptosis is associated with radiation sensitive HPV-positive HNSCC. Interestingly, we found that photodynamic therapy (PDT) directed at the endoplasmic reticulum (ER)/mitochondria initially induces paraptosis followed by apoptosis. This led to a substantial increase in radiation responsiveness in HPV-negative HNSCC, while the same PDT treatment had a minimal effect on HPV-positive cells. Here, we provide evidence that the autophagic adaptor p62 mediates signal relay for the induction of apoptosis, promoting ionizing radiation (XRT)-induced cell death in HPV-negative HNSCC. This work proposes that ER/mitochondria-targeted PDT can serve as a radiosensitizer in intrinsically radioresistant HNSCC that exhibits an increased autophagic flux.
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影响因子：
3.3
作者：
Carew JS;Kelly KR;Nawrocki ST
通讯作者：
Nawrocki ST
DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
--
作者：
Jung YS;Najy AJ;Huang W;Sethi S;Snyder M;Sakr W;Dyson G;Hüttemann M;Lee I;Ali-Fehmi R;Franceschi S;Struijk L;Kim HE;Kato I;Kim HC
通讯作者：
Kim HC
影响因子：
64.5
作者：
Jin, Zhaoyu;Li, Yun;Ashkenazi, Avi
通讯作者：
Ashkenazi, Avi
影响因子：
21.3
作者：
Cha-Molstad, Hyunjoo;Sung, Ki Sa;Hwang, Joonsung;Kim, Kyoung A.;Yu, Ji Eun;Yoo, Young Dong;Jang, Jun Min;Han, Dong Hoon;Molstad, Michael;Kim, Jung Gi;Lee, Yoon Jee;Zakrzewska, Adriana;Kim, Su-Hyeon;Kim, Sung Tae;Kim, Sun Yong;Lee, Hee Gu;Soung, Nak Kyun;Ahn, Jong Seog;Ciechanover, Aaron;Kim, Bo Yeon;Kwon, Yong Tae
通讯作者：
Kwon, Yong Tae