Dataset Information

Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.

ABSTRACT:

Background

Non-small-cell lung cancer (NSCLC) is categorized into various histologic subtypes that play an important role in prognosis and treatment outcome. We investigated the antitumor activity of motesanib, a selective antagonist of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, platelet-derived growth factor receptor, and Kit, alone and combined with chemotherapy in five human NSCLC xenograft models (A549, Calu-6, NCI-H358, NCI-H1299, and NCI-H1650) containing diverse genetic mutations.

Results

Motesanib as a single agent dose-dependently inhibited tumor xenograft growth compared with vehicle in all five of the models (P?ConclusionsThese data demonstrate that motesanib had antitumor activity against five different human NSCLC xenograft models containing diverse genetic mutations, and that it had enhanced activity when combined with cisplatin or docetaxel. These effects appeared to be mediated primarily by antiangiogenic mechanisms.

SUBMITTER: Coxon A

PROVIDER: S-EPMC3515409 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.

Coxon Angela A Ziegler Beth B Kaufman Stephen S Xu Man M Wang Hongyu H Weishuhn Dawn D Schmidt Joanna J Sweet Heather H Starnes Charlie C Saffran Douglas D Polverino Anthony A

Molecular cancer 20120919

<h4>Background</h4>Non-small-cell lung cancer (NSCLC) is categorized into various histologic subtypes that play an important role in prognosis and treatment outcome. We investigated the antitumor activity of motesanib, a selective antagonist of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, platelet-derived growth factor receptor, and Kit, alone and combined with chemotherapy in five human NSCLC xenograft models (A549, Calu-6, NCI-H358, NCI-H1299, and NCI-H1650) containing div ...[more]

PMID: 22992329

Similar Datasets

Project description:Background: Despite the recent approval of new oral therapies for the treatment of multiple sclerosis (MS), a significant percentage of patients are still not free from disease activity. In view of the complex pathogenesis and the relapsing and progressive nature of MS, combination therapy, a classical approach to treat many chronic diseases, could improve disease control over monotherapy. Ponesimod, a selective and rapidly reversible sphingosine-1-phosphate receptor Type 1 (S1P1) modulator, currently in Phase III clinical trial stage in relapsing MS (RMS), and dimethyl fumarate (DMF) would potentially be an ideal combination due to their differing mechanisms of action and oral administration. Objective: The goal of the study was to evaluate the therapeutic effect of ponesimod monotherapy and investigate the potential additive, or synergistic, activity of ponesimod-DMF combination therapy in experimental autoimmune encephalomyelitis (EAE) animal models of MS. Methods: Efficacy was evaluated in the myelin oligodendrocyte glycoprotein (MOG)-induced EAE model in C57BL/6 mice (ponesimod monotherapy) and in the myelin basic protein (MBP)-induced EAE model in Lewis rats (monotherapies and combination therapy). The principal readout was the clinical score assessing paralysis. Additional readouts, such as histopathology, survival, and disease prevalence, were generated in parallel when applicable. Results: Ponesimod monotherapy in the mouse EAE model showed significant efficacy in both preventative and therapeutic settings. In the rat EAE model, ponesimod demonstrated significant dose-dependent efficacy on clinical scores, while DMF showed only modest activity. Combination therapy synergistically reduced the severity and prevalence of disease. Only the combination treatment of ponesimod and DMF fully suppressed clinical disease activity by the end of the study. Conclusion: The results support the potential therapeutic benefits of combining ponesimod with DMF to improve disease activity control in patients with MS. Additionally, the results suggest that combining ponesimod with other oral agents that have different mechanisms of action might also be therapeutically beneficial to patients with MS.

Dataset Information

Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.

Background

Results

Publications

Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets