TY - JOUR

T1 - Boron-containing nucleosides as tools for boron-neutron capture therapy

AU - Zharkov, Dmitry O.

AU - Yudkina, Anna

AU - Riesebeck, Tim

AU - Loshchenova, Polina S.

AU - Mostovich, Evgeny A.

AU - Dianov, Grigory L.

N1 - This study was supported by the Russian Sci-ence Foundation grant number 19-74-20069 to GLD.

PY - 2021

Y1 - 2021

N2 - Despite the significant progress in cancer cure, the development of new approaches to cancer therapy is still of great importance since many deadly tumors remain untreatable. Boron neutron capture therapy (BNCT), proposed more than eighty years ago, is still considered a potentially advantageous approach. Irradiation of cells containing B-10 isotopes with epithermal neutrons and the consequent decay of boron nuclei releases particles that deposit high energy along a very short path, inflicting heavy damage on the target cells but sparing the neighbouring tissue. Delivery and preferential accumulation of boron in cancer cells are the major obstacles that slow down the clinical use of BNCT. Since DNA damage caused by irradiation is the major reason for cell death, the incorporation of boron-containing nucleotides into the DNA of cancer cells may significantly increase the efficacy of BNCT. In this review, we discuss the current state of knowledge in the synthesis of boron-containing nucleosides and their application for BNCT with a special focus on their possible incorporation into genomic DNA.

AB - Despite the significant progress in cancer cure, the development of new approaches to cancer therapy is still of great importance since many deadly tumors remain untreatable. Boron neutron capture therapy (BNCT), proposed more than eighty years ago, is still considered a potentially advantageous approach. Irradiation of cells containing B-10 isotopes with epithermal neutrons and the consequent decay of boron nuclei releases particles that deposit high energy along a very short path, inflicting heavy damage on the target cells but sparing the neighbouring tissue. Delivery and preferential accumulation of boron in cancer cells are the major obstacles that slow down the clinical use of BNCT. Since DNA damage caused by irradiation is the major reason for cell death, the incorporation of boron-containing nucleotides into the DNA of cancer cells may significantly increase the efficacy of BNCT. In this review, we discuss the current state of knowledge in the synthesis of boron-containing nucleosides and their application for BNCT with a special focus on their possible incorporation into genomic DNA.

KW - Boron neutron capture therapy

KW - therapeutic nucleosides

KW - carboranes

KW - DNA damage

KW - DNA repair

KW - drug metabolism

KW - HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE

KW - 3-CARBORANYL THYMIDINE ANALOGS

KW - NUCLEOTIDE EXCISION-REPAIR

KW - THYMINE DNA-GLYCOSYLASE

KW - BIOLOGICAL EVALUATION

KW - DELIVERY AGENTS

KW - EXONUCLEASE ACTIVITY

KW - POLYMERASE-EPSILON

KW - DRUG-RESISTANCE

KW - CANCER

M3 - Review article

VL - 11

SP - 4668

EP - 4682

JO - American journal of cancer research

JF - American journal of cancer research

SN - 2156-6976

IS - 10

ER -