EORTC-related new drug discovery and development activities: role of the Pharmacology and Molecular Mechanisms Group

Abstract

The EORTC Pharmacology and Molecular Mechanism Group (PAMM) focuses on applied research to translate basic/fundamental research discoveries in cancer biology into new drug discovery and development. PAMM provides a unique platform on the pharmacology, pharmacokinetics, pharmacodynamics of drug effects, molecular mechanisms of anticancer agents, and drug-related molecular pathology. For these purposes the group stimulates the interaction between basic scientists and clinicians in order to perform translational research on the pharmacology and molecular mechanisms of anticancer agents in Europe. The group has extensive expertise in various disciplines of pharmacology and has developed standards for studies performed in conjunction with clinical trials equivalent to those of good laboratory practice (GLP). The group serves as master organization for other EORTC (sub-)committees in the maximal interest of these groups and of the EORTC as a whole. PAMM merged with Preclinical Therapeutics Models Group (PTMG) in 2000 and with the Screening and Pharmacology Group (SPG) in 2003. The latter group continued as the Drug Discovery Committee within PAMM. The groups have always been involved in the development of anticancer agents, evolving from platinum analogs, anthracyclines, nitrosoureas, antifolates in the 1980's, to drugs derived from natural sources (trabectedin, taxanes) in the 1990's, and anti-signaling drugs, DNA alkylators, in the last decade. Several of these drugs have been registered. Mechanistic studies focused on drug activation/inactivation, target (DNA, receptors) in relation to efficacy and toxicity such as with several antimetabolites (5-fluorouracil, methotrexate), topoisomerase inhibitors (irinotecan), tyrosine kinase inhibitors (imatinib), acridones (C-1311), etc. The group recently included pharmacogenetics in the identification of genetic polymorphisms in order to use this information for personalized therapy.