Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma

Author:

Cho Won Jin,Kessel DavidORCID,Rakowski JosephORCID,Loughery Brian,Najy Abdo J.,Pham Tri,Kim Seongho,Kwon Yong Tae,Kato Ikuko,Kim Harold E.,Kim Hyeong-Reh C.ORCID

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.

Funder

National Institutes of Health

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Cited by 12 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. The dual role of autophagy in HPV-positive head and neck squamous cell carcinoma: a systematic review;Journal of Cancer Research and Clinical Oncology;2024-01-31

2. Targeting paraptosis in cancer: opportunities and challenges;Cancer Gene Therapy;2024-01-04

3. Photodynamic Therapy and Applications in Cancer;Recent Progress in Pharmaceutical Nanobiotechnology: A Medical Perspective;2023-12-27

4. Lipid-Coated Polymeric Nanoparticles for the Photodynamic Therapy of Head and Neck Squamous Cell Carcinomas;Pharmaceutics;2023-10-02

5. Manipulate tumor hypoxia for improved photodynamic therapy using nanomaterials;European Journal of Medicinal Chemistry;2023-02

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