Stapled peptide targeting the CDK4/Cyclin D interface combined with Abemaciclib inhibits KRAS mutant lung cancer growth - Institut Albert Bonniot Accéder directement au contenu
Article Dans Une Revue Theranostics Année : 2020

Stapled peptide targeting the CDK4/Cyclin D interface combined with Abemaciclib inhibits KRAS mutant lung cancer growth

Résumé

CDK4/cyclin D kinase constitutes an attractive pharmacological target for development of anticancer therapeutics, in particular in KRAS-mutant lung cancer patients, who have a poor prognosis and no targeted therapy available yet. Although several ATP-competitive inhibitors of CDK4 have been developed for anticancer therapeutics, they suffer from limited specificity and efficacy. Methods: As an alternative to ATP-competitive inhibitors we have designed a stapled peptide to target the main interface between CDK4 and cyclin D, and have characterized its physico-chemical properties and affinity to bind cyclin D1. Results: We have validated a positive correlation between CDK4/cyclin D level and KRAS mutation in lung cancer patients. The stapled peptide enters cells rapidly and efficiently, and inhibits CDK4 kinase activity and proliferation in lung cancer cells. Its intrapulmonary administration in mice enables its retention in orthotopic lung tumours and complete inhibition of their growth when co-administered with Abemaciclib. Conclusion: The stapled peptide targeting the main interface between CDK4 and cyclin D provides promising therapeutic perspectives for patients with lung cancer.

Domaines

Cancer
Fichier principal
Vignette du fichier
v10p2008.pdf (3.53 Mo) Télécharger le fichier
v10p2008s1.pdf (1.89 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

inserm-02440284 , version 1 (15-01-2020)

Identifiants

Citer

Céline Bouclier, Matthieu Simon, Guillaume Laconde, Morgan Pellerano, Sebastien Diot, et al.. Stapled peptide targeting the CDK4/Cyclin D interface combined with Abemaciclib inhibits KRAS mutant lung cancer growth. Theranostics, 2020, 10 (5), pp.2008-2028. ⟨10.7150/thno.40971⟩. ⟨inserm-02440284⟩
238 Consultations
181 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More