Molecular Epidemiology of the Main Druggable Genetic Alterations in Non-Small Cell Lung Cancer

Abstract

Lung cancer is the leading cause of death for malignancy worldwide. Its molecular profiling has enriched our understanding of cancer initiation and progression and has become fundamental to provide guidance on treatment with targeted therapies. Testing the presence of driver mutations in specific genes in lung tumors has thus radically changed the clinical management and outcomes of the disease. Numerous studies performed with traditional sequencing methods have investigated the occurrence of such mutations in lung cancer, and new insights regarding their frequency and clinical significance are continuously provided with the use of last generation sequencing technologies. In this review, we discuss the molecular epidemiology of the main druggable genetic alterations in non-small cell lung cancer, namely EGFR, KRAS, BRAF, MET, and HER2 mutations or amplification, as well as ALK and ROS1 fusions. Furthermore, we investigated the predictive impact of these alterations on the outcomes of modern targeted therapies, their global prognostic significance, and their mutual interaction in cases of co-occurrence.

Traditional herbal medicine combined with first-line platinum-based chemotherapy for advanced non-small-cell lung cancer

“…[ 2 , 3 ] In addition, molecular epidemiologic studies have shown that druggable mutations or PD-L1 positivity are found in no more than 50% of NSCLC patients. [ 6 , 30 ] Therefore, most patients still rely on platinum-based chemotherapy as a first-line therapy. Although its efficacy and benefits are well proven, side effects of platinum-based chemotherapy, including myelosuppression, nausea and vomiting, nephrotoxicity, ototoxicity, and peripheral neuropathy, also exist, some of which may even be fatal.…”

“…[ 4 ] In addition, targeted therapies or immunotherapies are applicable in less than half of cases. [ 5 , 6 ] Therefore, conventional chemotherapy regimens for NSCLC rely on platinum-based agents as the first-line treatment. [ 7 ]…”

Analysis of Copy Number Variations in Solid Tumors Using a Next Generation Sequencing Custom Panel

“…Despite this fact and the relatively small size of our cohort, the spectrum of CNVs observed in our study was coincident with previous reports. Thus, ERRB2, MET, or EGFR amplifications were frequently found in CRC while FGFR1 and EGFR CNVs were present in a small but significant percentage of lung tumors [17][18][19][20].…”

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

“…The presence of HER2 mutations is defined by a molecular subset of NSCLC with specific clinical-pathological features. These tumors occur in a higher frequency in Asian populations, women, nonsmokers, and in an adenocarcinoma histology even with bronchioalveolar features, a high morphological grade, TTF-1 positive staining, and a peculiar clinical presentation (disseminated lung nodules and tumor excavation), but they seem to have a similar survival compared with other molecularly defined cohorts [231,232]. Despite the higher prevalence in these specific subgroups of patients, HER2 mutations may be found too in men and heavy smokers.…”