Targeting Infrequent Driver Alterations in Non-Small Cell Lung Cancer

Marie-Julie Nokin; Chiara Ambrogio; Ernest Nadal; David Santamaria

doi:10.1016/j.trecan.2020.11.005

Targeting Infrequent Driver Alterations in Non-Small Cell Lung Cancer

Trends Cancer. 2021 May;7(5):410-429. doi: 10.1016/j.trecan.2020.11.005. Epub 2020 Dec 9.

Authors

Marie-Julie Nokin¹, Chiara Ambrogio², Ernest Nadal³, David Santamaria⁴

Affiliations

¹ University of Bordeaux, INSERM U1218, ACTION Laboratory, IECB, 33600 Pessac, France.
² Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
³ Department of Medical Oncology, Catalan Institute of Oncology, Clinical Research in Solid Tumors (CReST) Group, Oncobell Program, IDIBELL, L'Hospitalet, Barcelona, Spain. Electronic address: esnadal@iconcologia.net.
⁴ University of Bordeaux, INSERM U1218, ACTION Laboratory, IECB, 33600 Pessac, France. Electronic address: d.santamaria@iecb.u-bordeaux.fr.

PMID: 33309239
DOI: 10.1016/j.trecan.2020.11.005

Abstract

The discovery of oncogenic driver mutations led to the development of targeted therapies with non-small cell lung cancer (NSCLC) being a paradigm for precision medicine in this setting. Nowadays, the number of clinical trials focusing on targeted therapies for uncommon drivers is growing exponentially, emphasizing the medical need for these patients. Unfortunately, similar to what is observed with most targeted therapies directed against a driver oncogene, the clinical response is almost always temporary and acquired resistance to these drugs invariably emerges. Here, we review the biology of infrequent genomic actionable alterations in NSCLC as well as the current and emerging therapeutic options for these patients. Mechanisms leading to acquired drug resistance and future challenges in the field are also discussed.

Keywords: NSCLC; drug resistance; infrequent drivers; targeted therapy.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Carcinogenesis / drug effects
Carcinogenesis / genetics
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / immunology
Carcinoma, Non-Small-Cell Lung / mortality
Clinical Trials as Topic
Drug Resistance, Neoplasm / drug effects
Drug Resistance, Neoplasm / genetics
Drug Synergism
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics
Lung Neoplasms / immunology
Lung Neoplasms / mortality
Molecular Targeted Therapy / methods
Mutation
Precision Medicine / methods*
Progression-Free Survival
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins / antagonists & inhibitors*
Proto-Oncogene Proteins / genetics

Substances

Immune Checkpoint Inhibitors
Protein Kinase Inhibitors
Proto-Oncogene Proteins