Reference Detail

Ref Type

Journal Article

PMID

(39199558)

Authors

Decaudin D, Némati F, Masliah Planchon J, Seguin-Givelet A, Lefevre M, Etienne V, Ahnine H, Peretti Q, Sourd L, El-Botty R, Huguet L, Lagha S, Hegarat N, Roman-Roman S, Bièche I, Girard N, Montaudon E

Title

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancers	16	16	2024 Aug 07		Cancers (Basel)

URL

Abstract Text

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.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
HRAS G12S	lung squamous cell carcinoma	sensitive	Cisplatin + Pemetrexed Disodium + Trametinib	Preclinical - Pdx	Actionable	In a preclinical study, the addition of Mekinist (trametinib) to treament with the combination of Alimta (pemetrexed disodium) and Platinol (cisplatin) resulted in improved tumor growth inhibition compared to chemotherapy or Mekinist (trametinib) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring HRAS G12S (PMID: 39199558).	39199558
CDKN2A S12* PIK3CA E542K	lung squamous cell carcinoma	sensitive	Carboplatin + Paclitaxel + Palbociclib	Preclinical - Pdx	Actionable	In a preclinical study, the addition of Ibrance (palbociclib) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Ibrance (palbociclib) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring PIK3CA E542K and CDKN2A S12* (PMID: 39199558).	39199558
PTEN Q245*	lung squamous cell carcinoma	sensitive	Carboplatin + Paclitaxel + Vistusertib	Preclinical - Pdx	Actionable	In a preclinical study, the addition of Vistusertib (AZD2014) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Buparlisib (BKM120) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring PTEN Q245* (PMID: 39199558).	39199558
PIK3CA E542K	lung squamous cell carcinoma	sensitive	Buparlisib + Carboplatin + Paclitaxel	Preclinical - Pdx	Actionable	In a preclinical study, the addition of Buparlisib (BKM120) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Buparlisib (BKM120) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring PIK3CA E542K and CDKN2A S12* (PMID: 39199558).	39199558
HRAS G12S	lung squamous cell carcinoma	sensitive	Buparlisib + Carboplatin + Paclitaxel	Preclinical - Pdx	Actionable	In a preclinical study, the addition of Buparlisib (BKM120) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Buparlisib (BKM120) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring HRAS G12S (PMID: 39199558).	39199558
PTEN Q245*	lung squamous cell carcinoma	sensitive	Buparlisib + Carboplatin + Paclitaxel	Preclinical - Pdx	Actionable	In a preclinical study, the addition of Buparlisib (BKM120) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Buparlisib (BKM120) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring PTEN Q245* (PMID: 39199558).	39199558