Tackling Osimertinib Resistance in EGFR-Mutant Non–Small Cell Lung Cancer

Author:

Blaquier Juan Bautista1ORCID,Ortiz-Cuaran Sandra2ORCID,Ricciuti Biagio3ORCID,Mezquita Laura456ORCID,Cardona Andrés Felipe789ORCID,Recondo Gonzalo110ORCID

Affiliation:

1. 1Thoracic Oncology Unit, Medical Oncology, Center for Medical Education and Clinical Research (CEMIC), Buenos Aires, Argentina.

2. 2Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, Lyon, France.

3. 3Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

4. 4Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain.

5. 5Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain.

6. 6Department of Medicine, University of Barcelona, Barcelona, Spain.

7. 7Foundation for Clinical and Applied Cancer Research-FICMAC, Bogotá, Colombia.

8. 8Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad el Bosque, Bogotá, Colombia.

9. 9Direction of Research and Education, Luis Carlos Sarmiento Angulo Cancer Treatment and Research Cancer-CTIC, Bogotá, Colombia.

10. 10Medical Oncology Department, Bradford Hill Clinical Research Center, Santiago, Chile.

Abstract

AbstractThe current landscape of targeted therapies directed against oncogenic driver alterations in non–small cell lung cancer (NSCLC) is expanding. Patients with EGFR-mutant NSCLC can derive significant benefit from EGFR tyrosine kinase inhibitor (TKI) therapy, including the third-generation EGFR TKI osimertinib. However, invariably, all patients will experience disease progression with this therapy mainly due to the adaptation of cancer cells through primary or secondary molecular mechanisms of resistance. The comprehension and access to tissue and cell-free DNA next-generation sequencing have fueled the development of innovative therapeutic strategies to prevent and overcome resistance to osimertinib in the clinical setting. Herein, we review the biological and clinical implications of molecular mechanisms of osimertinib resistance and the ongoing development of therapeutic strategies to overcome or prevent resistance.

Funder

Instituto de Salud Carlos III

Sociedad Española de Oncología Médica

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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