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.