Abstract
Lung cancer has long been recognized as an extremely heterogeneous disease, since its development is unique in every patient in terms of clinical characterizations, prognosis, response and tolerance to treatment. Personalized medicine refers to the use of markers to predict which patient will most likely benefit from a treatment. In lung cancer, the well-developed epidermal growth factor receptor (EGFR) and the newly emerging EML4-anaplastic lymphoma kinase (ALK) are important therapeutic targets. This review covers the basic mechanism of EGFR and EML4-ALK activation, the predictive biomarkers, the mechanism of resistance, and the current targeted tyrosine kinase inhibitors. The efficacy of EGFR and ALK targeted therapies will be discussed in this review by summarizing the prospective clinical trials, which were performed in biomarker-based selected patients. In addition, the revolutionary sequencing and systems strategies will also be included in this review since these technologies will provide a comprehensive understanding in the molecular characterization of cancer, allow better stratification of patients for the most appropriate targeted therapies, eventually resulting in a more promising personalized treatment. The relatively low incidence of EGFR and ALK in non-Asian patients and the lack of response in mutant patients limit the application of the therapies targeting EGFR or ALK. Nevertheless, it is foreseeable that the sequencing and systems strategies may offer a solution for those patients.
Highlights
Lung cancer has the highest mortality rate of all cancers, and is the second most diagnosed cancer in both men and women, behind prostate and breast cancer, respectively [1,2,3]
NSCLC could be further divided into squamous cell carcinoma (SCC), adenocarcinoma and large cell lung carcinoma (LCLC)
KRAS mutations are a negative predictor of response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), mainly accounting for primary resistance [53]
Summary
Lung cancer has the highest mortality rate of all cancers, and is the second most diagnosed cancer in both men and women, behind prostate and breast cancer, respectively [1,2,3]. Despite the 5-year survival rate reaching 53% for patients diagnosed at an early stage, only 15% of such cases were determined in a timely manner when the tumor was still localized [2]. The inception of the human genome project gave birth to “personalized medicine” in cancer care treatment. This revolutionary method promises to help patients improve outcomes, avoid unnecessary treatments and reduce health care cost [8]. Personalized targeted therapy has already been applied towards the treatment of various cancers such as: NSCLC, squamous-cell carcinoma of the head and neck [10], colorectal cancer [11], pancreatic cancer [12], and breast cancer [13]. Revolutionary sequencing and systems strategies will be reviewed since we expect these methodologies to make personalized medicine a reality by looking at whole genome sequencing and the possible aberrations, rather than just one target (such as EGFR, KRAS or EML4-ALK)
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