PMID- 35471558
OWN - NLM
STAT- MEDLINE
DCOM- 20220826
LR  - 20221004
IS  - 1439-099X (Electronic)
IS  - 0179-7158 (Print)
IS  - 0179-7158 (Linking)
VI  - 198
IP  - 9
DP  - 2022 Sep
TI  - Kinase inhibitors increase individual radiation sensitivity in normal cells of 
      cancer patients.
PG  - 838-848
LID - 10.1007/s00066-022-01945-y [doi]
AB  - PURPOSE: Kinase inhibitors (KI) are known to increase radiosensitivity, which can 
      lead to increased risk of side effects. Data about interactions of commonly used 
      KI with ionizing radiation on healthy tissue are rare. PATIENTS AND METHODS: 
      Freshly drawn blood samples were analyzed using three-color FISH (fluorescence in 
      situ hybridization) to measure individual radiosensitivity via chromosomal 
      aberrations after irradiation (2 Gy). Thresholds of 0.5 and 0.6 breaks/metaphase 
      (B/M) indicate moderate or clearly increased radiosensitivity. RESULTS: The 
      cohorts consisted of healthy individuals (NEG, n = 219), radiosensitive patients 
      (POS, n = 24), cancer patients (n = 452) and cancer patients during KI therapy 
      (n = 49). In healthy individuals radiosensitivity (>/= 0.6 B/M) was clearly 
      increased in 5% of all cases, while in the radiosensitive cohort 79% were 
      elevated. KI therapy increased the rate of sensitive patients (>/= 0.6 B/M) to 35% 
      significantly compared to 19% in cancer patients without KI (p = 0.014). 
      Increased radiosensitivity of peripheral blood mononuclear cells (PBMCs) among 
      patients occurred in six of seven KI subgroups. The mean B/M values significantly 
      increased during KI therapy (0.47 +/- 0.20 B/M without compared to 0.50 +/- 0.19 B/M 
      with KI, p = 0.047). CONCLUSIONS: Kinase inhibitors can intensify individual 
      radiosensitivity of PBMCs distinctly in 85% of tested drugs.
CI  - (c) 2022. The Author(s).
FAU - Jost, Tina
AU  - Jost T
AUID- ORCID: 0000-0001-8767-3774
AD  - Department of Radiation Oncology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany. 
      tina.jost@uk-erlangen.de.
AD  - Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany. 
      tina.jost@uk-erlangen.de.
FAU - Schuster, Barbara
AU  - Schuster B
AD  - Department of Radiation Oncology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany.
FAU - Heinzerling, Lucie
AU  - Heinzerling L
AD  - Clinic and Polyclinic for Dermatology and Allergology, University Hospital 
      Munchen, Ludwig-Maximilian-Universitat (LMU), Munich, Germany.
FAU - Weissmann, Thomas
AU  - Weissmann T
AD  - Department of Radiation Oncology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
FAU - Fietkau, Rainer
AU  - Fietkau R
AD  - Department of Radiation Oncology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
FAU - Distel, Luitpold V
AU  - Distel LV
AUID- ORCID: 0000-0002-8040-3226
AD  - Department of Radiation Oncology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
FAU - Hecht, Markus
AU  - Hecht M
AUID- ORCID: 0000-0003-2082-216X
AD  - Department of Radiation Oncology, University Hospital Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
LA  - eng
PT  - Journal Article
DEP - 20220426
PL  - Germany
TA  - Strahlenther Onkol
JT  - Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et 
      al]
JID - 8603469
SB  - IM
MH  - Chromosome Aberrations
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Leukocytes, Mononuclear
MH  - Lymphocytes/radiation effects
MH  - *Neoplasms/radiotherapy
MH  - Radiation Tolerance
PMC - PMC9402507
OTO - NOTNLM
OT  - Blood
OT  - Chromosomal aberrations
OT  - Fluorescence in situ hybridization
OT  - Small molecules
OT  - Targeted therapy 
COIS- T. Jost, B. Schuster, L. Heinzerling, T. Weissmann, R. Fietkau and L.V. Distel 
      declare that they have no competing interests. M. Hecht reports collaborations 
      outside this project with Merck Serono (advisory role, speakers' bureau, 
      honoraria, travel expenses, research funding); MSD (advisory role, speakers' 
      bureau, honoraria, travel expenses, research funding); AstraZeneca (research 
      funding); Novartis (research funding); BMS (advisory role, honoraria, speakers' 
      bureau); Teva (travel expenses).
EDAT- 2022/04/27 06:00
MHDA- 2022/08/27 06:00
PMCR- 2022/04/26
CRDT- 2022/04/26 12:52
PHST- 2022/01/12 00:00 [received]
PHST- 2022/04/03 00:00 [accepted]
PHST- 2022/04/27 06:00 [pubmed]
PHST- 2022/08/27 06:00 [medline]
PHST- 2022/04/26 12:52 [entrez]
PHST- 2022/04/26 00:00 [pmc-release]
AID - 10.1007/s00066-022-01945-y [pii]
AID - 1945 [pii]
AID - 10.1007/s00066-022-01945-y [doi]
PST - ppublish
SO  - Strahlenther Onkol. 2022 Sep;198(9):838-848. doi: 10.1007/s00066-022-01945-y. 
      Epub 2022 Apr 26.