title: Trends in the early investigational drug development and areas for improvement.
abstract: The continuous discovery of 'druggable' protein involved in different signal transduction pathways and aberrant tumorigenic processes, has led to rapid progress in drug development. Nowadays several agents interfering with intriguing pathways are in early- and late-phase clinical development. Alteration in the cyclin-dependent kinase-retinoblastoma protein pathway is frequent in various types of cancer. In breast cancer, CDK 4/6 inhibitors have shown robust anticancer potencies, both in in vitro and in vivo studies. Numerous PI3K inhibitors have been developed and are in varying stages of clinical testing involving different and complementary therapeutic strategies in an effort to circumvent multiple pathway redundancies and pathway crosstalk. The molecular chaperone heat shock protein 90 targeted inhibition could lead to the blockade of multiple oncogenic signaling pathways in tumor cells, making it an attractive opportunity in the treatment of human malignancies. The acquired resistance to EGFR-tyrosine kinase inhibitors stimulates the development of several new drugs. Finally, among promising molecules, Janus-associated kinase inhibitors have been found to play a crucial role in the pathophysiology of cancer in combination with traditional and/or experimental treatment. This editorial gives an overview on the state-of-art development of different strategies in the targeted therapies scenario.
authors.affiliation: Campus Bio-Medico University of Rome, Medical Oncology , Rome , Italy g.tonini@unicampus.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D015507:Drugs, Investigational / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D015507:Drugs, Investigational; D018841:HSP90 Heat-Shock Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D053612:Janus Kinases; D018844:Cyclin-Dependent Kinases
keywords: CDK4/6 inhibitor; EGFR inhibitor; Hsp90 inhibitor; JAK inihibitor; PI3K inhibitor; target therapy