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

作者：Vari Sabrina; Pilotto Sara; Maugeri Sacca Marcello; Ciuffreda Ludovica; Incani Ursula Cesta; Falcone Italia; Del Curatolo Anais; Ceribelli Anna; Gelibter Alain; De Maria Ruggero; Tortora Giampaolo; Cognetti Francesco; Bria Emilio; Milella Michele^*

来源：Expert Opinion on Drug Discovery, 2013, 8(11): 1381-1397.

DOI：10.1517/17460441.2013.843523

• 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

Introduction: Non-small-cell lung cancer (NSCLC) subtypes are driven by specific 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 %26apos;driver%26apos; molecular aberrations are being discovered at an unprecedented pace. %26lt;br%26gt;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. %26lt;br%26gt;Expert opinion: Target identification and validation in NSCLC still requires considerable effort, as not all of the molecular alterations are clear %26apos;drivers%26apos; 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 development, aiming at the validation of an ideal %26apos;biology-to-trial%26apos; approach. Despite significant challenges, a truly %26apos;personalized%26apos; approach to NSCLC therapy appears to be within our reach.

• 出版日期2013-11