Identification of mutations in oncogenes associated with non-squamous (NSCLC) can help guide targeted therapy. Currently the most important oncogene, which is now routinely sought with genetic profiling assays, is epidermal growth factor receptor (EGFR). This protein stimulates tyrosine kinase. EFGR over expression and mutations in the tyrosine kinase domain of the EGFR gene can directly lead to tumour growth and progression; therefore, EGRF has itself become a target for chemotherapy and a number of specific agents have been developed that prevent activation, block the relevant signalling pathways and improve response rates to therapy. The relevant EGFR mutations, associated with sensitivity to tyrosine kinase inhibitors, are most commonly encountered in non-smoking females with adenocarcinoma. Therefore the detection of these mutations will predict a response rate of up to 70%, making targeted therapy prescription of these relatively costly treatments more cost-effective.

K-Ras

This protein stimulates signalling pathways downstream from EGFR. Specific mutations lead to the production of activated K-Ras protein, which continues to stimulate tumour growth. Although tyrosine kinase may block EGFR activation, it does not block the activity of mutated K-Ras proteins. Therefore patients with specific K-Ras mutations will not respond to tyrosine kinase inhibitors. Identification of K-Ras mutations is more common in smoking patients with adenocarcinoma, usually Caucasian rather than Asian. K-Ras mutations confer a poor prognostic outlook.

ALK

Mutations within the anaplastic lymphoma kinase (ALK) gene are associated with NSCLC (usually adenocarcinoma). Patients with ALK specific rearrangements do not benefit from tyrosine kinase inhibitors but may respond favourably to other therapies such as crizotinib, the first approved ALK inhibitor. 

There are a number of other mutations of potential importance in non-cell lung cancer. These can only be identified by molecular testing, which in turn may allow targeted therapy or prediction of resistance. EGRF, K-Ras and ALK mutations are usually mutually exclusive. Application of lung cancer mutation panel tests is therefore becoming increasingly commonplace, particularly as funding for this investigation becomes more widely approved.

责任编辑：admin