Lung cancer histology-driven strategic therapeutic approaches

Abstract

In the last decades, the dichotomic distinction between small cell (SCLC) and non-small cell lung cancer (NSCLC) has been one of the key parameters in the therapeutic management of lung cancer. However, the advent of targeted therapies based on druggable oncogenic molecular alterations and immunotherapy interfering with the PD1/PD-L1 checkpoint has overridden the role of the precise definition of tumour histologic type in the modern approach to lung cancer, particularly in NSCLC. While a better definition of histotype in NSCLC may be still helpful in selecting chemotherapy regimens in those NSCLC lacking targetable genetic alterations (i.e., EGFR and BRAF mutations, ALK and ROS1 rearrangements) and PD-L1 overexpression, the possible identification of targetable oncogenic drivers in liquid biopsy using high throughput deep sequencing methods will somehow change the paradigm of histology determination as one the mandatory step in future therapeutic strategies in lung cancer. Thus, in this review we challenge the future role of histotype as an important influencing factor in the clinical management of patients with NSCLC.