Special Issue "Targeted Therapy"
A special issue of Pharmaceuticals (ISSN 1424-8247).
Deadline for manuscript submissions: closed (28 February 2010).
Interests: computational medicinal chemistry; structure-based ligand design & discovery; modeling and simulation of targets and ligand-target complexes of therapeutic interest; chemical biology
In the last decade, the increased knowledge of the molecular determinants of cancer has boosted the search for the so-called “targeted drugs”, some of which are now clinically available, whereas many more are in clinical trials. Within this definition, we include both small organic molecules and monoclonal antibodies that, differently from the traditional chemotherapeutic agents, are able to recognize and bind specific protein targets in the diseased cells, such to impair their functioning and leading the cells to death. Great advantages in terms of improved efficacy and reduced toxicity can thus be achieved, as imatinib and bevacizumab have shown in the treatment of leukemias and solid tumors. However, the great expectations raised by the introduction of these innovative drugs are not fully satisfied, and, actually, the success rate is slower than predicted. Reasons for this are being presently explored, and one of them might reside just in the definition of the approach: in fact, defining the “target” against which to direct a chemical agent is crucial in determining the success or the failure of the intervention. There is a consensus nowadays on the idea that targeting a single protein is not enough to impair the myriad of interconnected events at the basis of the cellular life and development. Rather, it seems mandatory to identify and target one or more network of intracellular interactions to achieve a lethal interference with vital processes of the cancer cells. Accordingly, the present efforts towards the discovery of novel anticancer agents are firmly based on the acquired molecular knowledge of the biology of cancer, but aim at interrupting at multiple levels cellular pathways deemed as important and specific for the cells. Target identification and validation, molecular design, and advanced organic synthesis are key activities for the discovery of new clinical candidates, while the identification of biomarkers and the design of innovative clinical trials are fundamental for properly and quickly assessing the clinical efficacy of the new agents. The present Special Issue of “Pharmaceuticals” aims at collecting contributes reporting on the discovery and/or development of “targeted agents”, as well as on methods and approaches followed to meet this aim.
Prof. Dr. Maurizio Recanatini
- receptor kinases
- intracellular signaling
- cell cycle regulation
- protein dynamics
- kinase inhibitors
- epigenetic modulators
- proapoptotic agents