Recent advances in the biology of heavy-ion cancer therapy.
Superb biological effectiveness and dose conformity represent a rationale for heavy-ion therapy, which has thus far achieved good cancer controllability while sparing critical normal organs. Immediately after irradiation, heavy ions produce dense ionization along their trajectories, cause irreparable clustered DNA damage, and alter cellular ultrastructure. These ions, as a consequence, inactivate cells more effectively with less cell-cycle and oxygen dependence than conventional photons. The modes of heavy ion-induced cell death/inactivation include apoptosis, necrosis, autophagy, premature senescence, accelerated differentiation, delayed reproductive death of progeny cells, and bystander cell death. This paper briefly reviews the current knowledge of the biological aspects of heavy-ion therapy, with emphasis on the authors' recent findings. The topics include (i) repair mechanisms of heavy ion-induced DNA damage, (ii) superior effects of heavy ions on radioresistant tumor cells (intratumor quiescent cell population, TP53-mutated and BCL2-overexpressing tumors), (iii) novel capacity of heavy ions in suppressing cancer metastasis and neoangiogenesis, and (iv) potential of heavy ions to induce secondary (especially breast) cancer.
Hamada
Nobuyuki
N
Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, Komae, Tokyo, Japan. hamada-n@criepi.denken.or.jp
Imaoka
Tatsuhiko
T
Masunaga
Shin-ichiro
S
Ogata
Toshiyuki
T
Okayasu
Ryuichi
R
Takahashi
Akihisa
A
Kato
Takamitsu A
TA
Kobayashi
Yasuhiko
Y
Ohnishi
Takeo
T
Ono
Koji
K
Shimada
Yoshiya
Y
Teshima
Teruki
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001943:Breast Neoplasms / Q000209:etiology; D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002877:Chromosomes, Human / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D015870:Gene Expression / Q000528:radiation effects; D019254:Genes, bcl-2; D016158:Genes, p53; D063193:Heavy Ion Radiotherapy; D020450:Heavy Ions / Q000009:adverse effects; D006801:Humans; D018499:Linear Energy Transfer; D008297:Male; D009154:Mutation; D009362:Neoplasm Metastasis / Q000532:radiotherapy; D009369:Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D009389:Neovascularization, Pathologic / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000235:genetics