Current status of research and treatment for non-small cell lung cancer in never-smoking females

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide with over 1 million deaths each year. The overall prognosis of lung cancer patients remains unsatisfactory, with a 5-year overall survival rate of less than 15%. Although most lung cancers are a result of smoking, approximately 25% of lung cancer cases worldwide are not attributable to tobacco use. Notably, more than half of the lung cancer cases in women occur in non-smokers. Among non-small-cell lung cancer (NSCLC) cases, cigarette-smokers have a greater association with squamous cell carcinoma than adenocarcinoma, which is more common in non-smokers. These findings imply that specific molecular and pathological features may associate with lung adenocarcinoma arising in non-smoker female patients. Over the past decade, whole genome sequencing and other '-omics' technologies led to the discovery of pathogenic mutations that drive tumor cell formation. These technological developments may enable tailored patient treatments throughout the course of their disease, potentially leading to improved patient outcomes. Some clinical and laboratory studies have shown success outcomes using epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) in patients with EGFR mutations and ALK rearrangements, respectively. In fact, these 2 mutations are predominantly present in female non-smokers with adenocarcinoma. Immunotherapy has also recently emerged as a major therapeutic modality in NSCLC. In this review, we summarize the current understanding of NSCLC biology and new therapeutic molecular targets, focusing on the pathogenesis of non-smoker female NSCLC patients.

Keywords: ALK; EGFR; molecular subtypes; non-small cell lung cancer; non-smoker women.

Figure 1.

These charts indicate the difference frequencies of oncogenic drivers in smoking vs. never-smoking lung cancer.