Introduction
Lung cancer is one of the most frequent and deadly cancers worldwide. In the United States, approximately 230,000 patients are diagnosed with lung cancer and it is known to cause over 135,000 deaths annually [1]. Tobacco smoking is known to be the most common etiology for lung cancer accounting for approximately 80% of the lung cancer cases in the United States and other countries where smoking is common [2].However, 20% of lung cancer cases occur in patients who have never smoked, most commonly in women from East Asia, and has been associated with environmental exposures such as second-hand smoking, pollution and occupational carcinogens [3-5]. In 2010, data from the National Lung Screening Trial (NLST)showed that screening with low-dose helical CT scans in highrisk patients as compared with chest radiography resulted in significant reduction in the rates of both death from lung cancer (20%) and death from any cause (6.7%) [6-8].
The understanding of the biology and oncogenic mechanisms in lung cancer has greatly expanded in the last 20 years. This has led to the development of new biomarker-targeted therapies andimmune checkpoint inhibitors, with or without cytotoxic therapy regimens,for use in patients without targetable mutations.In an exploratory analysis conducted by Lung cancer mutation consortium, nearly 64% of 1007 patients with advanced lung adenocarcinoma were found to have targetable oncogenic drivers. Patients with driver mutations who received targeted therapies were found to have longer overall survival (OS) as compared to those with targetable mutation who did not receive targeted treatments or those without driver mutations (median survival, 3.5 years vs. 2.4 years and 2.1 years, respectively). [9] In the future, ongoing efforts to improve precision diagnosis by determining additional novel molecular markers and targeted therapies will continue to broaden the patient spectrum with advanced NSCLC patients who can benefit from these treatments and further improve clinical outcomes.
Since histologic features allow subtyping and molecular analysis of lung cancers and determine the major treatment options, a pathological diagnosis is essential.
There are various histological subtypes of NSCLC with adenocarcinoma (60%) being the most common type followed by squamous cell carcinoma (15%). NSCLC favoring adenocarcinoma is characterized by IHC staining positive for thyroid transcription factor 1 and cytokeratin 7 and negative for small cell cancer markers. NSCLC favoring squamous cell carcinoma is characterized by tumor markers negative for adenocarcinoma and positive for p63, cytokeratin 5, or cytokeratin 6. The tumor is classified as NSCLC, not otherwise specified (NOS) if all the above markers are negative. [10].
In this review, we provide an overview of the recent advances made in understanding the disease biology, mechanisms of tumor progression and multimodal treatment of metastatic NSCLC.