Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

Abstract

Genomic and proteomic mutation analysis is the standard of care for selecting candidates for therapies with tyrosine kinase inhibitors against the human epidermal growth factor receptor (EGFR TKI therapies) and further monitoring cancer treatment efficacy and cancer development. Acquired resistance due to various genetic aberrations is an unavoidable problem during EGFR TKI therapy, leading to the rapid exhaustion of standard molecularly targeted therapeutic options against mutant variants. Attacking multiple molecular targets within one or several signaling pathways by co-delivery of multiple agents is a viable strategy for overcoming and preventing resistance to EGFR TKIs. However, because of the difference in pharmacokinetics among agents, combined therapies may not effectively reach their targets. The obstacles regarding the simultaneous co-delivery of therapeutic agents at the site of action can be overcome using nanomedicine as a platform and nanotools as delivery agents. Precision oncology research to identify targetable biomarkers and optimize tumor homing agents, hand in hand with designing multifunctional and multistage nanocarriers that respond to the inherent heterogeneity of the tumors, may resolve the challenges of inadequate tumor localization, improve intracellular internalization, and bring advantages over conventional nanocarriers.

Targeted EGFR Nanotherapy in Non-Small Cell Lung Cancer

“…In addition, around 20–30% of NSCLC with an activating mutation display an intrinsic resistance to EGFR-TKI, the fast mutational characteristics leading to 50% resistance to first- and second-generation EGFR-TKIs within 9 to 14 months. To improve the EGFR inhibition, targeting several parts within the EGFR cascade or several parallel pathways to prevent cross-activation of the EGFR have been considered [ 156 , 157 ].…”