The distribution of these mutations has been found to be race-dependent, with one study estimating that 10% of Caucasians, but 50% of Asians, will be found to have such tumor markers. A number of different EGFR mutations have been discovered, but certain aberrations result in hyperactive forms of the protein. People with these mutations are more likely to have adenocarcinoma histology and be nonsmokers or light smokers. These people have been shown to be sensitized to certain medications that block the EGFR protein known as tyrosine kinase inhibitors specifically, erlotinib, gefitinib, afatinib, or osimertinib. Reliable identification of mutations in lung cancer needs careful consideration due to the variable sensitivity of diagnostic techniques. ALK gene rearrangements
Up to 7% of NSCLC patients have EML4-ALK translocations or mutations in the ROS1 gene; these patients may benefit from ALK inhibitors, which are now approved for this subset of patients. Crizotinib, which gained FDA approval in August 2011, is an inhibitor of several kinases, specifically ALK, ROS1, and MET. Crizotinib has been shown in clinical studies to have response rates around 60% if patients are shown to have ALK-positive disease. Several studies have also shown that ALK mutations and EGFR activating mutations are typically mutually exclusive. Thus, patients who fail crizotinib are not recommended to be switched to an EGFR-targeted drug such as erlotinib. Other treatment options
NSCLC patients with advanced disease who are not found to have either EGFR or ALK mutations may receive bevacizumab, which is a monoclonal antibody medication targeted against the vascular endothelial growth factor (VEGF).
Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively (neoadjuvant chemotherapy) and postoperatively (adjuvant chemotherapy). Types
The most common types of NSCLC are squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma, but several other types occur less frequently. A few of the less common types are pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma. All types can occur in unusual histologic variants and as mixed cell-type combinations. Nonsquamous-cell carcinoma almost occupies the half of NSCLC. In the tissue classification, the central type contains about one-ninth.Sometimes, the phrase "not otherwise specified" (NOS) is used generically, usually when a more specific diagnosis cannot be made. This is most often the case when a pathologist examines a small number of malignant cells or tissue in a cytology or biopsy specimen.Lung cancer in people who have never smoked is almost universally NSCLC, with a sizeable majority being adenocarcinoma.On relatively rare occasions, malignant lung tumors are found to contain components of both SCLC and NSCLC. In these cases, the tumors are classified as combined small-cell lung carcinoma (c-SCLC), and are (usually) treated as "pure" SCLC. Lung adenocarcinoma
Adenocarcinoma of the lung is currently the most common type of lung cancer in "never smokers" (lifelong nonsmokers). Adenocarcinomas account for about 40% of lung cancers.