[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-342758-105":59,"doc-detail-342758-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","a-perspective-on-tumor-radiation-resistance-following-high-let-radiation-treatment","A perspective on tumor radiation resistance following high-LET radiation treatment","","High-linear energy transfer (LET) radiation offers therapeutic advantages over conventional low-LET radiation by creating complex, clustered DNA lesions that can better drive cancer cell damage. A major obstacle remains the development of radiation resistance, whose molecular drivers may include translesion synthesis (TLS), replication gap suppression (RGS), autophagy, EMT activation, exosome release, and epigenetic alterations. The work discusses clustered DNA damage types, repair pathways, mutagenic outcomes, and resistance strategy development.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-perspective-on-tumor-radiation-resistance-following-high-let-radiation-treatment/342758/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-perspective-on-tumor-radiation-resistance-following-high-let-radiation-treatment/342758.png","ImageObject",300,407,{"name":92,"@type":93},"Aurora","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is high-LET radiation considered promising compared with low-LET radiation?","Question",{"text":112,"@type":113},"High-LET radiation induces complex, clustered DNA lesions, which can increase therapeutic effectiveness against cancer compared with sparsely ionizing low-LET radiation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What molecular mechanisms may contribute to radiation resistance after high-LET treatment?",{"text":117,"@type":113},"Potential contributors include translesion synthesis (TLS), replication gap suppression (RGS), autophagy, EMT activation, exosome release, and epigenetic changes.",{"name":119,"@type":110,"acceptedAnswer":120},"What are clustered DNA lesions and why do they matter for DNA repair?",{"text":121,"@type":113},"Clustered lesions involve multiple types of DNA damage in very close proximity, creating a significant challenge for the cell’s DNA repair machinery and helping explain the higher relative biological effectiveness of high-LET radiation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},342758,1790198821,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},4810365810221,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Journal of Cancer Research and Clinical Oncology (2024) 150:226  \n[https://doi.org/10.1007/s00432-024-05757-8](https://doi.org/10.1007/s00432-024-05757-8)  \nA perspective on tumor radiation resistance following high‑LET radiation treatment  \nYogendra Singh Rajpurohit1,2 · Dhirendra Kumar Sharma1 · Mitu Lal1 · Ishu Soni2  \nReceived: 24 February 2024 / Accepted: 22 April 2024 / Published online: 2 May 2024  \n© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024  \nAbstract  \nHigh-linear energy transfer (LET) radiation is a promising alternative to conventional low-LET radiation for therapeutic gain against cancer owing to its ability to induce complex and clustered DNA lesions. However, the development of radiation resistance poses a significant barrier. The potential molecular mechanisms that could confer resistance development are translesion synthesis (TLS), replication gap suppression (RGS) mechanisms, autophagy, epithelial-mesenchymal transition (EMT) activation, release of exosomes, and epigenetic changes. This article will discuss various types of complex clustered DNA damage, their repair mechanisms, mutagenic potential, and the development of radiation resistance strategies. Furthermore, it highlights the importance of careful consideration and patient selection when employing high-LET radiotherapy in clinical settings.  \nKeywords Linear energy transfer (LET) · Photon therapy · Relative biological effectiveness (RBE) · Clustered DNA lesions · Translesion synthesis (TLS)  \nOverview  \nCancer emerges as a worldwide health emergency, standing as a primary cause of both mortality and morbidity across the human population (Ferlay 2020). According to the World Health Organization (WHO), in 2020, there were approximately 18.1 million new cancer cases, resulting in 10 million deaths. The WHO predicts a staggering increase in cancer cases over the next two decades, estimating around 28 million cases by 2040. Furthermore, projections indicate 16.3 million deaths, marking a 63.7% increase from the statistics recorded in 2020 (Sung et al. 2021) . Thus, these findingsand estimates highlight the urgent need for effective cancer treatment strategies. A range of treatment modalities, such as surgery, radiation therapy (RT), chemotherapy, immunotherapy, targeted therapy, stem cell transplantation, natural antioxidants, nanoparticles, ablation therapy, radionics,  \n* Yogendra Singh Rajpurohit [ysraj@barc.gov.in](ysraj@barc.gov.in)  \n1 Molecular Biology Division, Bhabha Atomic Research Centre, 2-46-S, Modular Lab, A-Block, Mumbai 400085, India  \n2 Homi Bhabha National Institute, DAE-Deemed University, Mumbai 400094, India  \nchemodynamic therapy, ferroptosis and sonodynamic therapy, as well as multidisciplinary approaches, are utilized in the battle against cancer (Debela et al. 2021 ; Pucci et al. 2019 ; Arruebo et al. 2011 ; Moo et al. 2018) . Among these treatments, RT is a potent method, especially when combined with other treatment modalities. In principal, RT should be effective against all types of tumor cells. However, individual cells within tumors exhibit varying degrees of sensitivity to radiation, resulting in diverse treatment outcomes (Wang et al. 2018 ; Baskar et al. 2012) .  \nBiological responses triggered by radiation exposure depend on energy deposition per unit length of radiation track (keV/μm) known as linear energy transfer (LET), along with the cellular and tissue water activity and the composition of the extracellular matrix (ECM) . LowLET radiation (γ-rays and X-rays) is termed \"sparsely ionizing\" because it causes scattered ionizing events in various directions across space. In contrast, high-LET radiation, exemplified by protons (≤ 50 keV/µm), carbon ions (C-ions) (≤ 200 keV/µm), and alpha-emitting radionuclides (60 to 110 keV/μm), is referred to as \"densely ionizing\" because its ionizing effect predominantly occurs in the narrow region at the end of the primary path","cbCaifa9ziMPaUE2","https://ap.wps.com/l/cbCaifa9ziMPaUE2","pdf",1007063,15,"English","# Abstract\n# Overview\n## Cancer burden and need for effective treatments\n## Radiation therapy and LET-based biological effects\n## Complex clustered DNA damage and repair challenges\n## Development of radiation resistance mechanisms\n# Keywords","[{\"question\":\"Why is high-LET radiation considered promising compared with low-LET radiation?\",\"answer\":\"High-LET radiation induces complex, clustered DNA lesions, which can increase therapeutic effectiveness against cancer compared with sparsely ionizing low-LET radiation.\"},{\"question\":\"What molecular mechanisms may contribute to radiation resistance after high-LET treatment?\",\"answer\":\"Potential contributors include translesion synthesis (TLS), replication gap suppression (RGS), autophagy, EMT activation, exosome release, and epigenetic changes.\"},{\"question\":\"What are clustered DNA lesions and why do they matter for DNA repair?\",\"answer\":\"Clustered lesions involve multiple types of DNA damage in very close proximity, creating a significant challenge for the cell’s DNA repair machinery and helping explain the higher relative biological effectiveness of high-LET radiation.\"}]","A perspective on tumor radiation resistance following high-LET radiation treatment | PDF",1790048060,38]