Advances towards the design and development of personalized non-small-cell lung cancer drug therapy

Ruggero De Maria Marchiano, Emilio Bria, Sabrina Vari, Sara Pilotto, Marcello Maugeri-Saccà, Ludovica Ciuffreda, Ursula Cesta Incani, Italia Falcone, Anais Del Curatolo, Anna Ceribelli, Alain Gelibter, Francesco Cognetti, Michele Milella

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

4 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1381-1397
Numero di pagine17
RivistaExpert Opinion on Drug Discovery
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • 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

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