How Cells Clear TOP1cc Through Autophagy — And Why This Changes the Game for Anti-Cancer Discovery

A major Cell paper has uncovered a completely new layer of DNA repair biology: cells use selective autophagy and lysosomes to process and remove Topoisomerase I cleavage complexes (TOP1cc)—the toxic DNA–protein crosslinks created during normal replication and when cells are exposed to TOP1-targeting drugs like camptothecin. According to the Cell article (2024), researchers discovered that: […]

What a Creepy Looking Rodent Reveals about our Understanding of Longevity

What if the secret to slowing human aging isn’t a mystery at all, but a DNA repair trick stolen from a strange little creature that lives underground? A new Science paper just revealed something jaw-dropping: 👉 Naked mole-rats (also known as the sand puppy 😃) live ~40 years because their DNA repair machinery is turbo-charged […]

Dual-Target Inhibitors of DNA and TOP2A for the Treatment of Triple Negative Breast Cancer

They Said This Breast Cancer Was Untouchable. Now It’s 70% Gone! This is why TopoGEN is a key player, providing tools that allow anti-cancer drug discovery and facilitate such important findings. Scientists have designed a new “smart bomb” drug, DM1, that obliterates the deadliest form of breast cancer—triple-negative breast cancer—by hitting two critical targets at […]

Transfection-based HR and NHEJ kits: Now Available from TopoGEN

Transfection-based Homologous Recombination (HR)  and Non-homologous End Joining (NHEJ) kits use transient transfections to make a pool of cells containing the DNA reporters to allow the investigator to interrogate the 2 major DNA repair pathways. The advantages are:  It uses GFP readout to measure the efficiency of repair. There is zero background when repair is […]

Anthracycline drug targeting: cytoplasmic versus nuclear–a fork in the road.

The anthracycline antibiotics doxorubicin (Adriamycin; DOX) and daunorubicin (DNR) continue to be essential components of first-line chemotherapy in the treatment of a variety of solid and hematopoietic tumors. The overall efficacies of DOX and DNR are, however, impeded by serious dose-limiting toxicities, including cardiotoxicity, and the selection of multiple mechanisms of cellular drug resistance. These […]

DNA topoisomerase II rescue by catalytic inhibitors: a new strategy to improve the antitumor selectivity of etoposide.

The nuclear enzyme DNA topoisomerase II (topo II) is the target of important antitumor agents such as etoposide. Recent work has classified topo II targeting drugs into either topo II poisons that act by stabilizing enzyme-DNA cleavable complexes leading to DNA breaks, or topo II catalytic inhibitors that act at stages in the catalytic cycle […]

Topoisomerase I inhibitors: review and update.

This review presents a summary of preclinical and clinical data on the topoisomerase I (topo I) inhibitors that are under clinical development. To date, all of the topo I inhibitors that have been clinically evaluated are analogues of camptothecin, an extract of the Chinese tree Camptotheca acuminata. The therapeutic development of camptothecin was initially limited […]

The use of topoisomerase I inhibitors in multiple myeloma.

The standard treatment of multiple myeloma is systemic chemotherapy. Despite 30 years of drug development in myeloma, there are no new drug regimens significantly superior to melphalan and prednisone. In addition, phase II studies of new drugs in myeloma have been disappointing, with low response rates and no prolongation in survival. The topoisomerase I (topo […]

Mechanism of action of camptothecin.

Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-I, resulting in accumulation of a covalent reaction intermediate, […]

Dual topoisomerase I/II inhibitors in cancer therapy.

While the majority of topoisomerase (topo) inhibitors show selectivity against either topo I or topo II, a small class of compounds can act against both enzymes. These can be divided into three classes. The first and largest class comprise drugs that bind to DNA by intercalation and include the clinically-evaluated acridine DACA, the benzopyridoindole intoplicine, […]

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