Broad-spectrum cytotoxic drugs have been used in cancer therapy for decades. However, their lack of specificity to cancer cells often results in serious side-effects, limiting efficacy. For this reason, antibodies have been used to attempt to specifically target cytotoxic drugs to tumours. One such approach is antibody-directed enzyme prodrug thera...
Published in Oncotarget
The sequence asparagine-glycine arginine (NGR), flanked by Cysteine (Cys) residues so as to form a disulfide-bridge (CNGRC), has previously been found to target and bind specifically to aminopeptidase N (APN), which is highly expressed on the surface of tumor cells. The goal of this study was to develop and evaluate the potential of fusion proteins...
Published in Molecules
Access of proteins to their intracellular targets is limited by a hydrophobic barrier called the cellular membrane. Conjugation with cell-penetrating peptides (CPPs) has been shown to improve protein transduction into the cells. This conjugation can be either covalent or non-covalent, each with its unique pros and cons. The CPP-protein covalent con...
Published in Annales de biologie clinique
High-dose of methotrexate chemotherapy is used in the treatment of some tumors. It presents several side effects that required therapeutic drug monitoring, which is commonly performed on 24, 48 and 72h after the beginning of the methotrexate infusion. Treatment of overexposure to methotrexate is based on injection of carboxypeptidase G2, which spec...
Published in Thérapie
Le méthotrexate (MTX) est un cytotoxique prescrit à haute dose dans le traitement de pathologies cancéreuses. La co-prescription de MTX aux inhibiteurs de pompe à proton (IPP) est déconseillée pour des doses supérieures à 20 mg/semaine et seulement à prendre en compte pour les doses inférieures. La littérature rapporte de nombreux cas d’altération ...
Published in Gene Therapy of Cancer
Despite great achievements in cancer chemotherapy, restricting the toxic effects of chemotherapeutic agents to tumor cells in order to enhance efficacy and reduce side effects remains a major challenge. To overcome this challenge, suicide gene therapy or gene-directed enzyme prodrug therapy (GDEPT), which is an alternative two-step process to conve...
This is the report of a case of methotrexate nephrotoxicity for which glucarpidase was used. We use the case to review a number of teaching points related to this new treatment option.
Published in Therapeutics and clinical risk management
In January 2012, glucarpidase (Voraxaze(®)) received approval from the US Food and Drug Administration for intravenous treatment of toxic plasma methotrexate concentrations due to impaired renal clearance. Methotrexate, an antifolate agent, has been used for over 60 years in the treatment of various cancers. High-dose methotrexate has been particul...
Published in Journal of Medical Toxicology
Published in British Journal of Cancer
