DNA methylation pattern between patients with HER3+ and HER3- brain metastases
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA911674 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:HER3 (ErbB3) belongs to a family of receptor tyrosine kinases together with the known oncogenes EGFR and HER2. Recently, antibody drug conjugates (ADCs) targeting these receptors showed promising clinical activity in extracranial malignancies of breast and lung cancer. We aimed to investigate HER3 expression in breast and lung cancer brain metastases (BM) as the basis for future clinical trial design. Illumina MethylationEPIC 850k microarrays were used to analyze genome-wide DNA methylation patterns of HER3-positive (n=43) and HER3-negative (n=28) BM.
2023-03-31 | GSE220826 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE284054 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271580 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271579 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271742 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271740 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271739 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271738 | GEO
Project description:Genomic Characterization of Brain Metastases
| PRJNA578190 | ENA
Project description:Genomic Characterization of Brain Metastases
| PRJNA578191 | ENA