Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma
| Autor: | Abdo J. Najy, Brian Loughery, Seongho Kim, Yong Tae Kwon, Hyeong Reh Choi Kim, David Kessel, Joseph T. Rakowski, Ikuko Kato, Tri Pham, Won Jin Cho, Harold Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Radiosensitizer autophagy medicine.medical_treatment Photodynamic therapy lcsh:RC254-282 Article Paraptosis 03 medical and health sciences 0302 clinical medicine Radiation sensitivity stomatognathic system Radioresistance medicine otorhinolaryngologic diseases neoplasms business.industry apoptosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Head and neck squamous-cell carcinoma Radiation therapy stomatognathic diseases 030104 developmental biology Oncology photodynamic therapy 030220 oncology & carcinogenesis Cancer research paraptosis business ER/mitochondrial photosensitizer |
| Zdroj: | Cancers Volume 13 Issue 6 Cancers, Vol 13, Iss 1193, p 1193 (2021) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13061193 |
| Popis: | Simple Summary 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. Abstract 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. |
| Databáze: | OpenAIRE |
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