Genomic profiling of small-cell lung cancer: the era of targeted therapies

Abstract

The molecular profiling of small-cell lung cancer is challenging because of the difficulty in obtaining suitable tumor samples for integrative genomic analysis. While an urgent need exists for well-defined and effective therapeutic targets in small-cell lung cancer, no significant improvement has been made in treating this disease over the past 30 years. Recently, three reports describing comprehensive genomic analyses of small-cell lung cancer have been published. These reports have provided a framework of biologically relevant genes in small-cell lung cancer and have demonstrated that the genomic landscape of small-cell lung cancer was almost equivalent between Asian and Caucasian populations. Of note, these three comprehensive genomic analyses and other molecular analyses of small-cell lung cancer have contributed to the identification of patient populations that may benefit from promising targeted agents, such as those affecting the PI3K/AKT/mTOR pathway, FGFR1, RET or AURORA kinase inhibitors. Targeting small-cell lung cancer cells with tumor suppressor gene alteration based on synthetic lethality is also promising. The present review provides an overview of the biologically relevant genetic alterations and targeted therapies of small-cell lung cancer focusing on recent discoveries that could impact the management of small-cell lung cancer.

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

“…Cancer genomics using next generation sequencing technology have successfully characterized a number of therapeutic targets of lung cancer ( 1 – 6 ). EGFR mutations have been identified in more than 50% of lung adenocarcinomas (LADs) 2 from East Asian non-smokers, and these tumors have been termed oncogene-addicted to reflect their dependence on EGFR-mediated, prosurvival signaling ( 7 ).…”

Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway

“…As a highly malignant pulmonary neuroendocrine tumor, small-cell lung cancer (SCLC) represents 15% of all lung cancer with a high proliferative index and a strong possibility of early metastasis [1]. The prognosis of SCLC remains notably poor and therapeutic development has lagged behind non-small cell lung cancer (NSCLC) [2].…”

A recurrence-free survivor with chemotherapy-refractory small cell lung cancer after pneumonectomy

“…[ 13 ] Comprehensive genomic analysis of SCLC might be a choice to identify patients who could benefit from targeted therapy. [ 14 , 15 ]…”