A perspective on tumor radiation resistance following high-LET radiation treatment

• Published in: Journal of cancer research and clinical oncology Vol. 150; no. 5; p. 226
• Main Authors: Rajpurohit, Yogendra Singh, Sharma, Dhirendra Kumar, Lal, Mitu, Soni, Ishu
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 02-05-2024; Springer Nature B.V
• Subjects: Animals; Autophagy; Cancer Research; DNA damage; DNA Damage - radiation effects; DNA repair; DNA Repair - radiation effects; Epigenetics; Exosomes; Hematology; Humans; Internal Medicine; Linear Energy Transfer; Matters Arising; Medicine; Medicine & Public Health; Molecular modelling; Neoplasms - pathology; Neoplasms - radiotherapy; Oncology; Radiation therapy; Radiation Tolerance; Relative biological effectiveness (RBE); Photon therapy; Linear energy transfer (LET); Clustered DNA lesions; Translesion synthesis (TLS)
• ISSN: 1432-1335; 0171-5216; 1432-1335
• DOI: 10.1007/s00432-024-05757-8

High-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.