Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all

Radiation Oncology

Table 1 DNA damaging chemotherapeutic agents interacting with hyperthermia

Class	Agent [with references to studies showing interaction of the agent with hyperthermia]	Type of inflicted DNA damage	Pathways involved in repair [references]
Alkylating agents	- triazenes (temozolomide [182, 183])	strand cross-links, adducts, DSBs (indirect)	NER, BER, MMR, NHEJ, HR [108, 184]
	- nitrogen mustard derivatives (cyclophosphamide [13, 185–191], melphalan [191–199])
	- aziridine-containing (mitomycin C [10, 187, 191, 200–203])
Alkylating-like platinum compounds	- cisplatin [12, 100, 101, 191, 201, 204–210], carboplatin [211–214], oxaliplatin [198, 199, 209, 215]	strand cross-links, DSBs (indirect)	NER, BER, MMR, HR [94, 95, 216, 217]
Antimetabolites	- pyrimidine analogs (5-fluorouracil [218], gemcitabine [161, 199, 219])	SSBs, DSBs (indirect), oxidative damage	HR, MMR, NER [148, 161, 220, 221]
	- purine analogs (2-aminopurine [222], 6-thioguanine [222])
	- dihydrofolate reductase inhibitors (methotrexate [210, 223])
Topoisomerase I poisons	- camptothecin [224], B-lapachone [144, 145], Irinotecan [199]	SSBs	BER, NER, NHEJ [225, 226]
Topoisomerase II poisons	- intercalators (doxorubicin [187, 188, 227–230])	DSBs	NHEJ, HR [231–233]
Radiomimetics	- enediynes (neocarzinostatin [10])	SSBs, DSBs, oxidative damage, strand cross-links	HR, NHEJ, BER, [136, 137, 234, 235]
	- bleomycin [6, 10, 12, 191, 210, 236, 237]
	- mitomycin C [10, 187, 191, 200–203]
PARP inhibitors	- olaparib [150, 153], PJ-34 [150]	SSBs, DSBs (indirect)	HR, BER [238–240]

ISSN: 1748-717X