DNA topoisomerase II (for etoposide and doxorubicin), Microtubule (for microtubule-targeting agents), DNA (for DNA crosslinking and platinum adducts in cisplatin treatment) (Top2, MT (microtubule), DNA)

This class represents the principal molecular targets of traditional cytotoxic chemotherapeutic agents. DNA topoisomerase II is a nuclear enzyme essential for the maintenance of DNA topology during replication and transcription, targeted by agents like etoposide and doxorubicin to induce DNA strand breaks and apoptosis[5]. The microtubule, primarily composed of beta-tubulin, is a structural component critical for mitosis, targeted by taxanes and vinca alkaloids to disrupt spindle formation and cell division, leading to mitotic arrest and cell death[2][8]. DNA itself is directly targeted by agents such as cisplatin, which form crosslinks and adducts that impede replication and transcription, ultimately triggering apoptosis[3][9]. Chemoresistance is often mediated by increased DNA repair capacity and altered cellular signaling, and efficacy can be influenced by molecular or post-translational markers such as microtubule acetylation[1][4][6][7].

Other names

Topoisomerase IIBeta-tubulin (for microtubule, taxane, vinca targets)DNA (as a chemotherapeutic target by alkylating/platinum compounds)

Topoisomerase II inhibition (etoposide, doxorubicin): blocks religation of DNA leading to DNA breaks and apoptosis[5] - DNA intercalation (doxorubicin): inserts between DNA base pairs, disrupts DNA function - Free radical generation (doxorubicin): oxidative DNA damage - DNA crosslinking (cisplatin): induces intra- and inter-strand DNA crosslinks, blocking replication and transcription[3][9] - Platinum adduct formation (cisplatin): forms DNA-platinum covalent adducts, stalling replication - Microtubule polymerization/stabilization or destabilization: taxanes stabilize, vinca alkaloids destabilize, both lead to mitotic arrest and apoptosis[2][8]