Topoisomerasehemmer

Topoisomerase inhibitors, also known as Topoisomerasehemmer in German, are a class of anticancer drugs that target the DNA-relaxing enzymes topoisomerase I and II. These enzymes create transient breaks in DNA to relieve torsional stress during replication and transcription. Inhibitors stabilize these breaks or trap the enzymes on DNA, resulting in unrepaired strand breaks and cancer cell death.

Topoisomerase I inhibitors, such as irinotecan and topotecan, trap the enzyme–DNA complex after a single-strand break, preventing religation and leading to double-strand breaks during replication. Topoisomerase II inhibitors, including etoposide, doxorubicin, daunorubicin, and mitoxantrone, block re-ligation of double-strand breaks, causing DNA damage and cell death. Camptothecins (topo I inhibitors) and epipodophyllotoxins (topo II inhibitors) are key drug families within this class.

These agents are used across solid tumors and hematologic malignancies. Irinotecan and topotecan are commonly used for colorectal cancer and small cell lung cancer, respectively. Etoposide is a component of regimens for testicular cancer and lymphomas, while anthracyclines such as doxorubicin and daunorubicin are widespread in breast cancer, lymphomas, and other solid tumors.

Drug resistance can arise through reduced drug accumulation, altered topoisomerase, or enhanced DNA repair. Adverse effects include myelosuppression and nausea; topo I inhibitors often cause diarrhea (notably irinotecan), while topo II inhibitors carry risks of cardiotoxicity and mucositis. Pharmacogenetics, notably UGT1A1 variants, influence irinotecan toxicity due to differences in drug activation and clearance.

Research includes newer topo I inhibitors and nonclassic topo I inhibitors (such as indenoisoquinolines) with the aim of improved activity and reduced resistance or toxicity.