Tyrosine Kinase Receptor Landscape in Lung Cancer: Therapeutical Implications

Abstract

Lung cancer is a heterogeneous disease responsible for the most cases of cancer-related deaths. The majority of patients are clinically diagnosed at advanced stages, with a poor survival rate. For this reason, the identification of oncodrivers and novel biomarkers is decisive for the future clinical management of this pathology. The rise of high throughput technologies popularly referred to as "omics" has accelerated the discovery of new biomarkers and drivers for this pathology. Within them, tyrosine kinase receptors (TKRs) have proven to be of importance as diagnostic, prognostic, and predictive tools and, due to their molecular nature, as therapeutic targets. Along this review, the role of TKRs in the different lung cancer histologies, research on improvement of anti-TKR therapy, and the current approaches to manage anti-TKR resistance will be discussed.

Figure 1

Workflow of the identification and validation of biomarkers and therapeutic targets through omics techniques.

Figure 2

TKR alterations in lung cancer studies. Graphs showing the frequency of alterations in TKRs of relevance in the different lung cancer histologies found in different studies publicly available at http://www.cbioportal.org/. The different studies are designated by capital letters: (A) Imielinski et al., 2012 [5]; (B) MSKCC (Memorial Sloan Kettering Cancer Center) 2015; (C) TCGA, 2014 [6]; (D) Ding et al., 2008 [7]; (E) TCGA, 2012 [8]; (F) Peifer et al., 2012 [9]; (G) Rudin et al., 2012 [10]; and (H) George et al., Nature 2015 [11]. Only studies A, C, and E have information about copy number alterations. ADC: lung adenocarcinoma; SCC: lung squamous cell carcinoma; SCLC: small-cell lung cancer.