5-(4-amino-1-propan-2-yl-3-pyrazolo[3-4-d]pyrimidinyl)-1-3-benzoxazol-2-amine and Small-Cell-Lung-Carcinoma

5-(4-amino-1-propan-2-yl-3-pyrazolo[3-4-d]pyrimidinyl)-1-3-benzoxazol-2-amine has been researched along with Small-Cell-Lung-Carcinoma* in 2 studies

Other Studies

2 other study(ies) available for 5-(4-amino-1-propan-2-yl-3-pyrazolo[3-4-d]pyrimidinyl)-1-3-benzoxazol-2-amine and Small-Cell-Lung-Carcinoma

Article	Year
Simultaneously targeting DNA damage repair pathway and mTORC1/2 results in small cell lung cancer growth arrest via ER stress-induced apoptosis. International journal of biological sciences, 2018, Volume: 14, Issue:10 Topics: Apoptosis; Benzoxazoles; Cell Line, Tumor; DNA Damage; Endoplasmic Reticulum Stress; Humans; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Pyrazoles; Pyrimidines; Pyrimidinones; Small Cell Lung Carcinoma; TOR Serine-Threonine Kinases	2018
RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR. Oncotarget, 2017, Jan-24, Volume: 8, Issue:4 Small cell lung cancer (SCLC) is an aggressive cancer that represents ~15% of all lung cancers. Currently there are no targeted therapies to treat SCLC. Our genomic analysis of a metastatic SCLC cohort identified recurrent RICTOR amplification. Here, we examine the translational potential of this observation. RICTOR was the most frequently amplified gene observed (~14% patients), and co-amplified with FGF10 and IL7R on chromosome 5p13. RICTOR copy number variation correlated with RICTOR protein expression in SCLC cells. In parallel, cells with RICTOR copy number (CN) gain showed increased sensitivity to three mTOR inhibitors, AZD8055, AZD2014 and INK128 in cell growth assays, with AZD2014 demonstrating the best inhibition of downstream signaling. SCLC cells with RICTOR CN gain also migrated more rapidly in chemotaxis and scratch wound assays and were again more sensitive to mTOR inhibitors. The overall survival in SCLC patients with RICTOR amplification was significantly decreased (p = 0.021). Taken together, our results suggest that SCLC patients with RICTOR amplification may constitute a clinically important subgroup because of their potential response to mTORC1/2 inhibitors. Topics: Adult; Aged; Aged, 80 and over; Benzamides; Benzoxazoles; Female; Fibroblast Growth Factor 10; Gene Amplification; Humans; Interleukin-7 Receptor alpha Subunit; Lung Neoplasms; Male; Middle Aged; Molecular Targeted Therapy; Morpholines; Protein Kinase Inhibitors; Pyrimidines; Rapamycin-Insensitive Companion of mTOR Protein; Small Cell Lung Carcinoma; Survival Analysis; Treatment Outcome	2017

Article

Year

Simultaneously targeting DNA damage repair pathway and mTORC1/2 results in small cell lung cancer growth arrest via ER stress-induced apoptosis.

International journal of biological sciences, 2018, Volume: 14, Issue:10

Topics: Apoptosis; Benzoxazoles; Cell Line, Tumor; DNA Damage; Endoplasmic Reticulum Stress; Humans; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Pyrazoles; Pyrimidines; Pyrimidinones; Small Cell Lung Carcinoma; TOR Serine-Threonine Kinases

2018

RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR.

Oncotarget, 2017, Jan-24, Volume: 8, Issue:4

Small cell lung cancer (SCLC) is an aggressive cancer that represents ~15% of all lung cancers. Currently there are no targeted therapies to treat SCLC. Our genomic analysis of a metastatic SCLC cohort identified recurrent RICTOR amplification. Here, we examine the translational potential of this observation. RICTOR was the most frequently amplified gene observed (~14% patients), and co-amplified with FGF10 and IL7R on chromosome 5p13. RICTOR copy number variation correlated with RICTOR protein expression in SCLC cells. In parallel, cells with RICTOR copy number (CN) gain showed increased sensitivity to three mTOR inhibitors, AZD8055, AZD2014 and INK128 in cell growth assays, with AZD2014 demonstrating the best inhibition of downstream signaling. SCLC cells with RICTOR CN gain also migrated more rapidly in chemotaxis and scratch wound assays and were again more sensitive to mTOR inhibitors. The overall survival in SCLC patients with RICTOR amplification was significantly decreased (p = 0.021). Taken together, our results suggest that SCLC patients with RICTOR amplification may constitute a clinically important subgroup because of their potential response to mTORC1/2 inhibitors.

Topics: Adult; Aged; Aged, 80 and over; Benzamides; Benzoxazoles; Female; Fibroblast Growth Factor 10; Gene Amplification; Humans; Interleukin-7 Receptor alpha Subunit; Lung Neoplasms; Male; Middle Aged; Molecular Targeted Therapy; Morpholines; Protein Kinase Inhibitors; Pyrimidines; Rapamycin-Insensitive Companion of mTOR Protein; Small Cell Lung Carcinoma; Survival Analysis; Treatment Outcome

2017