Does the natural product, honokiol, have value in the battle against osimertinib resistance?

• Type of Material: Article
• Authors: Karin A. Vallega, Emory University; Shi-Yong Sun, Emory University
• Language: English
• Date: 2020-09-09
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Vallega and Sun.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncoscience.517
• Title of Journal or Parent Work: Oncoscience
• Volume: 7
• Issue: 9-10
• Start Page: 73
• End Page: 75
• Keywords: osimertinib; non-small cell lung cancer (NSCLC); targeted therapy; chemotherapy; epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs); death; lung cancer
• Research Categories: Health Sciences, Oncology; Health Sciences, Rehabilitation and Therapy

Abstract

Worldwide, lung cancer is the leading cause of cancer deaths. The invention of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized treatment for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. EGFR-TKIs are the first targeted therapy available for lung cancer, and show improvement over chemotherapy as a first-line treatment [1]. Unfortunately, the emergence of acquired resistance limits long-term benefits for patients. Resistance to early generations of EGFR-TKIs are predominately due to the appearance of the T790M resistance mutation, which accounts for 41-62% of relapse cases [1]. Third-generation EGFR-TKIs, such as osimertinib (AZD9291/TAGRISSOTM), were developed to target the acquired T790M mutation and the common activated mutations, such as 19del and L858R, while limiting activity against wild-type EGFR. Osimertinib is now approved as a second line treatment after acquired resistance to earlier EGFR-TKIs due to the T790 mutation, and as a first line treatment for NSCLC patients with the common activated EGFR mutations. It shows improved progression-free survival compared to earlier generation EGFR-TKIs [2] with the advantage of significantly improving overall survival [3]. However, acquired resistance to osimertinib has also emerged. On average, patients relapsed after 18.9 months when using osimertinib as a first-line treatment, and 10.1 months when used as a second-line treatment [2, 4]. Therefore, it is imperative to develop novel strategies to overcome osimertinib acquired resistance and increase patient survival and quality of life.