Abstract
The research and treatment of non-small cell lung cancer (NSCLC) have achieved some important advances in recent years. Nonetheless, the overall survival rates for NSCLC remain low, indicating the importance to effectively develop new therapies and improve current approaches. The understanding of the function of different biomarkers involved in NSCLC progression, survival and response to therapy are important for the development of early detection tools and treatment options. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (K-RAS) are two of the main significant biomarkers for the management of NSCLC. Mutations in these genes were associated with development and response to therapies. For example, the use of small molecule tyrosine kinase (TK) inhibitors and immunotherapy has led to benefits in some, but not all patients with altered EGFR. In contrast, there is still no effective approved drug to act upon patients harbouring K-RAS mutations. In addition, K-RAS mutations have been associated with lack of activity of TK inhibitors. However, promising approaches aimed to inhibit mutant K-RAS are currently under study. Therefore, this review will discuss these approaches and also EGFR therapies, and hopefully, it will draw attention to the need of continued research in the field in order to improve the outcomes in NSCLC patients.
Highlights
The world health organization (WHO) characterises lung cancer as the second leading cause of death in the world, being tobacco use the most important risk factor
Lung cancer arises from the cells of the respiratory epithelium and can be divided into: small cell lung cancer (SCLC), a highly malignant tumour derived from cells exhibiting neuroendocrine characteristics and accounts for 15% of lung cancer cases and non–small cell lung cancer (NSCLC), which corresponds to 85% of cases
The results showed high potency and selectivity towards K-RASG12C, showing rapid and sustained in vivo target occupancy to induce tumour regression [17]
Summary
The world health organization (WHO) characterises lung cancer as the second leading cause of death in the world (one in six deaths), being tobacco use the most important risk factor. The most common subtype of lung cancer is adenocarcinoma comprising approximately 40% of NSCLC cases, followed by squamous-cell carcinoma 25–30% and large cell (undifferentiated) carcinoma 5–10% [3]. The genomic profiling of tumours revolutionised medicine firstly by analysing tumour’s tissues and secondly by the less invasive option, the use of plasma genotyping to detect circulating tumour DNA (ctDNA). These collectively improved the identification of different genetic alterations and generated options for targeted therapies to support individualised treatment. The different strategies will be discussed in this review
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