Current Medicinal Chemistry - Volume 24, Issue 15, 2017

Amongst all currently used drugs in the field of cancer therapy, the most prominent group of agents which induce DNA, damage both directly or indirectly. Intuitively DNA should not be a perfect target for relatively unspecific small molecular weight drugs. However, the current understanding is that not damage per se but cellular response to DNA damage induced by antitumor agents is responsible for their specific targeted eff Read More

DNA-damaging drugs in cancer present two main problems: therapeutic resistance and side effects and both can associate with DNA repair, which can be targeted in cancer therapy. Bleomycin (BLM) induces complex DNA damages, including strand breaks, base loss and 3’-phosphoglycolate (3’PG) residues repaired by several pathways, but 3’PGs must be processed to the 3’-OH ends, usually by tyrosyl-DNA phosphodiesteras Read More

Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer t Read More

Platinum-based anti-cancer agents, which include cisplatin, carboplatin and oxaliplatin, are an important class of drugs used in clinical setting to treat a variety of cancers. The cytotoxic efficacy of these drugs is mediated by the formation of inter-strand and intrastrand crosslinks, or platinum adducts on nuclear DNA. There is also evidence demonstrating that mitochondrial DNA is susceptible to platinum-adduct damage in dors Read More

Colorectal cancer (CRC) is one the greatest contributors to cancer related mortality. Although 5 year survival rate for patients at the early stage of CRC (stages I and II) is above 60%, more than 50% of patients are diagnosed at or beyond stage III when distant metastasis has already occurred, in which case 5 year survival rate drops to 10%. Chemotherapeutic intervention coupled with surgery is the backbone of metastatic CRC Read More

Compounds causing DNA damage have been used widely in molecular biology and some are used as therapeutic agents in cancer therapy. In most cases, their cellular response is pleiotropic, making it challenging to develop these agents efficiently for potential therapeutic use. Furthermore, this means that such compounds can also affect healthy tissues, which is a major drawback for the use in therapy. Thus, dissecting and unde Read More

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are una Read More

Topoisomerases are ubiquitous enzymes involved in maintaining genomic stability of the cell by regulating the over- or underwinding of DNA strands. Besides their customary functions, topoisomerases are important cellular targets of widely used anticancer drugs. In particular, topoisomerase IIα (Top2α) has been postulated as the primary molecular target of anthracycline’s anticancer activity, whereas topoiso Read More