azd-6244 and Squamous-Cell-Carcinoma-of-Head-and-Neck

azd-6244 has been researched along with Squamous-Cell-Carcinoma-of-Head-and-Neck* in 2 studies

Other Studies

2 other study(ies) available for azd-6244 and Squamous-Cell-Carcinoma-of-Head-and-Neck

Article	Year
Differential mutation spectrum and immune landscape in African Americans versus Whites: A possible determinant to health disparity in head and neck cancer. Cancer letters, 2020, 11-01, Volume: 492 Topics: Adult; Aged; Benzimidazoles; Black or African American; DNA Methylation; Female; Head and Neck Neoplasms; Health Status Disparities; Humans; Male; Middle Aged; Mutation; Squamous Cell Carcinoma of Head and Neck; White People	2020
Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition. Cancer science, 2018, Volume: 109, Issue:12 Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor. Topics: Animals; Benzimidazoles; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Resistance, Neoplasm; Drug Synergism; Extracellular Signal-Regulated MAP Kinases; Fibroblast Growth Factor 2; Head and Neck Neoplasms; Humans; MAP Kinase Signaling System; Mice; Pyrimidines; Receptor, ErbB-3; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays	2018

Article

Year

Differential mutation spectrum and immune landscape in African Americans versus Whites: A possible determinant to health disparity in head and neck cancer.

Cancer letters, 2020, 11-01, Volume: 492

Topics: Adult; Aged; Benzimidazoles; Black or African American; DNA Methylation; Female; Head and Neck Neoplasms; Health Status Disparities; Humans; Male; Middle Aged; Mutation; Squamous Cell Carcinoma of Head and Neck; White People

2020

Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition.

Cancer science, 2018, Volume: 109, Issue:12

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.

Topics: Animals; Benzimidazoles; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Resistance, Neoplasm; Drug Synergism; Extracellular Signal-Regulated MAP Kinases; Fibroblast Growth Factor 2; Head and Neck Neoplasms; Humans; MAP Kinase Signaling System; Mice; Pyrimidines; Receptor, ErbB-3; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays

2018