Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer - Current Use and Future Prospects

Sep 21, 2026

Uploaded by Miles

Tyrosine kinase inhibitors (TKIs) are established as a leading targeted cancer therapy, designed to reduce adverse effects seen with non-targeted treatments, particularly injury to healthy cells. Resistance driven by EGFR mutations motivates four TKI generations, each improving efficacy and tolerability and yielding better patient outcomes. The review summarizes clinical evidence and mechanisms across generations, including advances against T790M and ongoing efforts to address newer resistance such as C797S, while noting emerging trial data and the need for additional studies before approval.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

Cancer

Treatment

Non-TKI Agents

Review Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer: Current Use and Future Prospects Henry Dickerson 1,†, Ahmad Diab 1,† and Othman Al Musaimi 1,2, * Citation: Dickerson, H.; Diab, A.; Al Musaimi, O. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer: Current Use and Future Prospects. Int. J. Mol. Sci. 2024, 25, 10008. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms251810008 Academic Editor: Jaw Ji Yang Received: 30 August 2024 Revised: 12 September 2024 Accepted: 16 September 2024 Published: 17 September 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK; [h.dickerson2@newcastle.ac.uk](h.dickerson2@newcastle.ac.uk) (H.D.); [a.diab2@newcastle.ac.uk](a.diab2@newcastle.ac.uk) (A.D.) 2 Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UK * Correspondence: [othman.almusaimi@newcastle.ac.uk](othman.almusaimi@newcastle.ac.uk) † These authors contributed equally to this work. Abstract: Tyrosine kinase inhibitors (TKIs) have emerged as a leading targeted cancer therapy, reducing the side effects often seen with non-targeted treatments, especially the damage to healthy cells. To tackle resistance, typically caused by epidermal growth factor receptor (EGFR) mutations, four generations of TKIs have been developed. Each generation has shown improved effectiveness and fewer side effects, resulting in better patient outcomes. For example, patients on gefitinib, a first-generation TKI, experienced a progression-free survival (PFS) of 10 months compared to 5 months with conventional chemotherapy. Second-generation TKI afatinib outperformed erlotiniband extended PFS to 11.1 months compared to 6.9 months with cisplatin. Third-generation TKIs further increased survival to 38.6 months, compared to 31.8 months with first-generation TKIs. This progress demonstrates the ability of newer TKIs to overcome resistance, particularly the T790M mutation, while reducing adverse effects. Ongoing research focuses on overcoming resistance from newer mutations like C797S to further improve patient survival. These developments highlight the significant progress in TKI therapy and the continued effort to refine cancer treatment. Recent research in South Korea shows that third-generation TKIs are ineffective against non-small cell lung cancer (NSCLC) with the C797S mutation. Several trials have started showing promising in vitro and in vivo results, but more trials are needed before clinical approval. This review underscores notable advancements in the field of EGFR TKIs, offering a comprehensive analysis of their mechanisms of action and the progression of various TKI generations in response to resistance. Keywords: tyrosine kinase inhibitors; epidermal growth factor receptors; NSCLC; gefitinib; afatinib 1. Introduction 1.1. Cancer The National Health Service (NHS) in the UK defines cancer as a condition where cells grow and reproduce uncontrollably, with the potential to spread to other body parts through metastasis. The most common cancers in the UK are breast, lung, prostate, and bowel cancer. Early symptoms often include a lump in the affected area. Diagnosis usually involves a combination of screening tests, urinalysis, and blood analysis, as no single test can definitively diagnose cancer [1,2] . In 2012, cancer caused a loss of 281,373 life years, with an average of 19.64 years per person. Productivity losses totaled USD 149 million for males and USD 121 million for females, with the top five cancers responsible for nearly half of

FAQs

What is the role of EGFR mutations in TKI resistance?

Resistance is often caused by EGFR mutations. The review links resistance to specific mutation-driven challenges that newer TKI generations attempt to overcome.

How do different generations of EGFR TKIs improve outcomes?

Each generation of TKIs is described as achieving improved effectiveness and fewer side effects compared with earlier options, with clinical examples of longer progression-free survival.

What ongoing research direction is highlighted for future TKI therapy?

The review emphasizes research to counter resistance from newer mutations such as C797S, supported by emerging in vitro and in vivo findings and the need for more trials before clinical approval.

Sep 21, 2026

Uploaded by Miles