EGFR targeted therapy in lung cancer; an evolving story

Abstract

Specific oncogenes with driver mutations, such as the Epidermal Growth Factor Receptor (EGFR 1) gene can lead to non-small-cell lung cancer formation. Identification of these oncogenes, their driver mutations and downstream effects allow the targeting of these pathways by drugs. Such personalised therapy has become an important strategy in combating lung cancer and highlights the need to test for these mutations. Tyrosine Kinase Inhibitors (TKIs) against EGFR, such as Erlotinib, are able to halt these tumour promoting properties in non-small-cell lung cancers. Third generation EGFR TKIs, such as Osimertinib, are focussing on resulting acquired TKI resistance. Here we report the clinical course of a patient with metastatic non-small-cell lung cancer who has undergone EGFR targeted therapy and been further challenged by TKI acquired resistance. Her extended survival and maintained quality of life are a consequence of these modern, genotype-targeted, personalised metastatic non-small-cell lung cancer therapies.

Genome‐scale CRISPR screening identifies cell cycle and protein ubiquitination processes as druggable targets for erlotinib‐resistant lung cancer

“…Many tyrosine kinase inhibitors (TKIs) have been developed to suppress the tumor-promoting properties caused by EGFR mutations in nonsmall-cell lung cancer (NSCLC) patients [4,5]. Among the EGFR-targeting TKIs, erlotinib is widely used for both localized and metastatic NSCLC patients [6,7] because it has relatively few side-effects and high efficacy [8]. However, many patients subsequently develop resistance to erlotinib treatment.…”

Precision medicine in relapsed or refractory pediatric solid tumors: a collaborative Spanish initiative

“…Nowadays, many pediatric institutions are starting to build molecular screening programs in order to treat patients according to their genomic alterations. The extent of genomic studies ranges from commercial hotspot cancer panels developed for adult tumours to whole exome sequencing (WES), RNA sequencing and methylation arrays [5,19]. Noteworthy, the exome represents approximately 1% of the genome and harbour about 85% of the disease driven mutations.…”

“…This has driven a rapid increase in molecular knowledge of tumors (especially in adults) [3], and as a result, the development of targeted treatments [4]. The new molecular targeted therapies have achieved unthinkable success in medical oncology, not so many years ago [5][6][7][8]. A significant percentage of adult patients may beneficiate from them after molecular tumor study [9].…”

Oncogenetics of Lung Cancer Induced by Environmental Carcinogens

“…Many of the single cancer-associated genes that are affected by exposure to these environmental agents are promising therapeutic intervention points. For instance, targeted inhibitors of EGFR (e.g., erlotinib, afatinib)-a protein transcribed from a gene commonly up-regulated upon exposure to arsenic-are used in lung cancer treatment to interfere with the aberrant growth pathways activated by the upregulation of this signaling receptor [130]. Additionally, the association between radon exposure and ALK gene rearrangements in lung cancer patients may be amenable to therapy with inhibitors of the ALK protein (e.g., crizotinib, ceritinib) [131].…”