2. Academic Validation
  3. Evaluation of Combined Chemotherapy and Genomic-Driven Targeted Therapy in Patient-Derived Xenografts Identifies New Therapeutic Approaches in Squamous Non-Small-Cell Lung Cancer Patients

Evaluation of Combined Chemotherapy and Genomic-Driven Targeted Therapy in Patient-Derived Xenografts Identifies New Therapeutic Approaches in Squamous Non-Small-Cell Lung Cancer Patients

  • Cancers (Basel). 2024 Aug 7;16(16):2785. doi: 10.3390/cancers16162785.
Didier Decaudin 1 2,  Fariba Némati 1,  Julien Masliah Planchon 3,  Agathe Seguin-Givelet 4 5,  Marine Lefevre 6,  Vesnie Etienne 1,  Harry Ahnine 1,  Quentin Peretti 1,  Laura Sourd 1,  Rania El-Botty 1,  Lea Huguet 1,  Sarah Lagha 2,  Nadia Hegarat 2,  Sergio Roman-Roman 7,  Ivan Bièche 3,  Nicolas Girard 2 8,  Elodie Montaudon 1
Affiliations

Affiliations

  • 1 Laboratory of Preclinical Investigation, Department of Translational Research, Institut Curie, PSL University Paris, 75005 Paris, France.
  • 2 Department of Medical Oncology, Institut Curie, 75005 Paris, France.
  • 3 Department of Genetic, Institut Curie, 75005 Paris, France.
  • 4 Department of Thoracic Surgery, Curie-Montsouris Thorax Institute, Institut Mutualiste Montsouris, 75014 Paris, France.
  • 5 Faculty of Medicine SMBH, Paris 13 University, Sorbonne Paris Cité, 75013 Bobigny, France.
  • 6 Department of Pathology, Institut Mutualiste Montsouris, 75014 Paris, France.
  • 7 Department of Translationnal Research, Institut Curie, PSL University Paris, 75006 Paris, France.
  • 8 Paris Saclay University, University of Versailles Saint-Quentin-en-Yvelines (UVSQ), 91405 Versailles, France.
PMID: 39199558 DOI: 10.3390/cancers16162785
Abstract

The combination of chemotherapy and targeted therapy has been validated in non-small-cell lung Cancer (NSCLC) patients with EGFR mutations. We therefore investigated whether this type of combined approach could be more widely used by targeting other genetic alterations present in NSCLC. PDXs were generated from patients with NSCLC adenocarcinomas (ADCs) and squamous-cell carcinomas (SCCs). Targeted NGS analyses identified various molecular abnormalities in the MAPK and PI3K pathways and in the cell cycle process in our PDX panel. The antitumor efficacy of targeted therapies alone or in combination with chemotherapy was then tested in vivo. We observed that trametinib, BKM120, AZD2014 and palbociclib increased the efficacy of each chemotherapy in SCC PDXs, in contrast to a non-insignificant or slight improvement in ADCs. Furthermore, we observed high efficacy of trametinib in KRAS-, HRAS- and NRAS-mutated tumors (ADCs and SCCs), suggesting that the MEK Inhibitor may be useful in a wider population of NSCLC patients, not just those with KRAS-mutated ADCs. Our results suggest that the detection of pathogenic variants by NGS should be performed in all NSCLCs, and particularly in SCCs, to offer patients a more effective combination of chemotherapy and targeted therapy.

Keywords

NGS-defined targeted therapy; PDXs; chemotherapy; combination; squamous NSCLC.

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