Table 1. . Drugs which have been used for second-line chemotherapy in high-grade osteosarcoma.

Drug	Main mechanism(s) of action
Vinca alkaloids (vinorelbine, vinblastine)	Binding to β-tubulin, inhibition of microtubules formation and microtubules destabilization Cell-cycle arrest and apoptosis induction
Taxanes (docetaxel, paclitaxel)	Binding to β-tubulin, microtubules stabilization and inhibition of their disassembly during mitosis Cell-cycle arrest and apoptosis induction
Gemcitabine	Cytidine analogue that blocks DNA synthesis during the S phase of cell cycle Cell-cycle arrest and apoptosis induction
Etoposide	Binding to both DNA and topoisomerase II, leading to single- and double-strand DNA breaks Inhibition of cell proliferation and apoptosis induction
Bleomycin	Induction of single- and double-strand DNA breaks G2/M cell cycle arrest and apoptosis induction
Dactinomycin (actinomycin D)	DNA intercalation and stabilization of cleavable complexes of topoisomerases I and II with DNA Formation of DNA single-strand breaks Inhibition of DNA replication and RNA transcription Inhibition of cell proliferation and apoptosis induction
Cyclophosphamide	Alkylation of DNA and formation of intrastrand and interstrand DNA crosslinks Interference with DNA replication and induction of apoptosis
Carboplatin	Formation of intra- and interstrand DNA crosslinks Inhibition of DNA replication and transcription and induction of apoptosis
Topotecan Irinotecan	Interaction with the topoisomerase I-DNA complex, leading to DNA damage Inhibition of DNA replication and transcription Inhibition of cell proliferation and apoptosis induction