TY - JOUR
T1 - Advances towards the design and development of personalized non-small-cell lung cancer drug therapy
AU - Vari, Sabrina
AU - Pilotto, Sara
AU - Maugeri-Saccà, Marcello
AU - Ciuffreda, Ludovica
AU - Cesta Incani, Ursula
AU - Falcone, Italia
AU - Del Curatolo, Anais
AU - Ceribelli, Anna
AU - Gelibter, Alain
AU - De Maria Marchiano, Ruggero
AU - Cognetti, Francesco
AU - Bria, Emilio
AU - Milella, Michele
PY - 2013
Y1 - 2013
N2 - ntroduction: Non-small-cell lung cancer (NSCLC) subtypes are driven by spe- cific genetic aberrations. For reasons such as this, there is a call for treatment personalization. The ability to instigate NSCLC fragmentation poses new methodological problems, and new ‘driver’ molecular aberrations are being discovered at an unprecedented pace.
Areas covered: This article describes the clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)-rearranged NSCLC. Further, the authors briefly describe the emerging molecular targets in NSCLC, in terms of both rationale for therapeutic targeting and strategies, for clinical development.
Expert opinion: Target identification and validation in NSCLC still requires considerable effort, as not all of the molecular alterations are clear ‘drivers’ nor can they be efficiently targeted with available drugs. However, 50% of the NSCLC cases are without clear-defined molecular aberrations. Clinical trial methodology will need to develop novel paradigms for targeted drug devel- opment, aiming at the validation of an ideal ‘biology-to-trial’ approach. Despite significant challenges, a truly ‘personalized’ approach to NSCLC ther- apy appears to be within our reach.
AB - ntroduction: Non-small-cell lung cancer (NSCLC) subtypes are driven by spe- cific genetic aberrations. For reasons such as this, there is a call for treatment personalization. The ability to instigate NSCLC fragmentation poses new methodological problems, and new ‘driver’ molecular aberrations are being discovered at an unprecedented pace.
Areas covered: This article describes the clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)-rearranged NSCLC. Further, the authors briefly describe the emerging molecular targets in NSCLC, in terms of both rationale for therapeutic targeting and strategies, for clinical development.
Expert opinion: Target identification and validation in NSCLC still requires considerable effort, as not all of the molecular alterations are clear ‘drivers’ nor can they be efficiently targeted with available drugs. However, 50% of the NSCLC cases are without clear-defined molecular aberrations. Clinical trial methodology will need to develop novel paradigms for targeted drug devel- opment, aiming at the validation of an ideal ‘biology-to-trial’ approach. Despite significant challenges, a truly ‘personalized’ approach to NSCLC ther- apy appears to be within our reach.
KW - AKT, ALK, clinical trial design, EGFR, FGFR, MAPK, MEK, Met, molecular characterization, mTOR, non-small-cell lung cancer, personalized therapy, PI3K, proteomics, PTEN, RAF, RAS, RET, ROS, signaling pathways
KW - AKT, ALK, clinical trial design, EGFR, FGFR, MAPK, MEK, Met, molecular characterization, mTOR, non-small-cell lung cancer, personalized therapy, PI3K, proteomics, PTEN, RAF, RAS, RET, ROS, signaling pathways
UR - http://hdl.handle.net/10807/111506
U2 - 10.1517/17460441.2013.843523
DO - 10.1517/17460441.2013.843523
M3 - Article
SN - 1746-0441
SP - 1381
EP - 1397
JO - Expert Opinion on Drug Discovery
JF - Expert Opinion on Drug Discovery
ER -