The PI3k inhibitors: New hopes in the battle against advanced NSCLC

Abstract

In terms of both incidence and mortality, lung tumor is the most common cancer in the world today. Among lung tumors, 80% are classified as non-small-cell lung cancer (NSCLC) and are mostly diagnosed at an advanced stage (either locally advanced or metastatic disease). Platinum-based doublet chemotherapy, the standard treatment for advanced NSCLC, has reached a plateau of effectiveness and achieves mostly partial responses in only 30%-40% of patients and a modest survival increase. Thus, the search for new molecularly targeted therapies is mandatory. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently over activated in human cancers playing a critical role both in the initiation and progression of NSCLC. Activating mutations of this pathway play a role in the development of resistance to chemotherapy and to the Epidermal Growth Factor Receptor Tyrosine Kinase inhibitors (EGFR-TKIs) erlotinib and gefitinib. These mutations are observed in 2-5% of non-squamous NSCLC and 8-10% of squamous NSCLC. In this paper, we describe the available data and the possible future role of PI3k inhibitors in the treatment of advanced NSCLC.