KIS - Prof. Kai Rothkamm - Radiation biomarkers in cancer therapy

Recording of the Kiel Imaging Seminar from 03/06/2024
Prof. Kai Rothkamm - Laboratory of Radiobiology & Experimental Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Abstract:
The response of cancer cells to radiotherapy and a number of chemotherapeutic agents is to a large extent determined by their ability to minimse DNA damage prior to entering critical cell cycle phases, i.e. S phase or mitosis. DNA double-strand breaks (DSBs) and other multiply damaged sites on the DNA are generally regarded as the most lethal type of DNA damage. Cells are able to repair most of the DSBs, but a few breaks may either remain unrepaired or end up being mis-repaired, resulting in replication stress as well as chromosome aberrations. Several DSB repair mechanisms have evolved and are strictly regulated in mammalian cells to ensure genome stability. However, in cancer cells the efficiency of individual repair pathways and/or their orchestration are often compromised. Biomarkers of radiation damage - such as physical DSB assays, gamma-H2AX or 53BP1 immunofluorescence foci, or dicentric chromosomes and acentric fragments - can be utilised to assess the treatment response of individual cancer cell lines or in fact ex-vivo-cultured tumour organoids or tissue slices. This knowledge not only improves our understanding of the mechanisms underlying the individual response to treatments such as radiotherapy but, importantly, also facilitates the identification of new tumour-specific therapeutic targets and implementation of personalised treatment strategies.
• Rothkamm K, Barnard S, Moquet J, Ellender M, Rana Z, Burdak-Rothkamm S. (2015). DNA damage foci: Meaning and significance. Environ Mol Mutagen. 2015 Jul;56(6):491-504.
• Burdak-Rothkamm S, Mansour WY, Rothkamm K. (2020). DNA Damage Repair Deficiency in Prostate Cancer. Trends Cancer. 2020 Nov;6(11):974-984.