STTT：华西医院魏霞蔚团队等发现克服肺癌放疗抵抗的新靶点

Core Viewpoint - Lung cancer is the most common cancer globally and a leading cause of cancer-related deaths. Radiation therapy (RT) is an effective method for controlling local tumors in lung cancer, but its long-term benefits are often compromised by radioresistance, leading to tumor recurrence. The development of targeted therapies has significantly improved the prognosis for lung cancer patients, particularly those with non-small cell lung cancer (NSCLC). However, inherent and acquired resistance to targeted drugs remains a challenge, and the complex interactions between targeted therapies and radiation therapy are a research focus. Therefore, understanding the molecular mechanisms of radioresistance in lung cancer and exploring the combination of targeted therapy with radiation therapy is urgent [1][4]. Group 1 - The study published by researchers from Sichuan University West China Hospital identifies the JMJD6/EHF signaling axis as a potential therapeutic target to overcome radioresistance in non-small cell lung cancer [2][3]. - The research aims to explore new mechanisms of tumor metastasis following radiation therapy in NSCLC patients and to enhance the durability of radiation therapy's efficacy [5]. - The study utilized human NSCLC tissue arrays, whole transcriptome sequencing, CUT&Tag sequencing, and single-cell RNA sequencing to identify gene expression changes induced by radiation therapy [5]. Group 2 - Results indicate that radiation therapy upregulates the expression of JMJD6 in NSCLC tissues, and high expression of JMJD6 is associated with reduced overall survival [5]. - This upregulation activates EHF and leads to the demethylation of H4R3me2s, subsequently transcribing pluripotency factor genes. The JMJD6/EHF signaling axis plays a critical role in the metastasis of NSCLC, potentially mediated through TGF-β/SMAD and AKT/ERK signaling pathways [5]. - These findings suggest that JMJD6 may serve as a potential therapeutic target against tumor metastasis following radiation therapy in non-small cell lung cancer [5].