GLPG0187 / Galapagos - LARVOL DELTA

The CTSZ-TRA2A-IL32 axis defines a targetable macrophage-dependent pathway in metastatic prostate cancer. (PubMed, J Transl Med) - "The CTSZ/TRA2A/IL-32/ITGA5 axis orchestrates protumoral immunity in PCa metastasis by driving M2-TAM recruitment. Targeting this pathway, particularly through ITGA5 blockade, represents a promising therapeutic strategy to inhibit metastatic progression and remodel the immunosuppressive tumor microenvironment."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IL32 • ITGA5

ITGAV Regulation of LGALS3BP-JUNB Axis Facilitates the Cell-to-Cell Adhesion and Invasiveness of Hepatic Cancer Cells. (PubMed, Anticancer Res) - "The LGALS3BP-JUNB axis regulates ITGAV expression and contributes to HCC progression. Targeting ITGAV, with LGALS3BP as a potential biomarker, and the combined inhibition of both LGALS3BP and ITGAV may represent a promising therapeutic strategy for HCC."

Biomarker • Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • ITGAV • JUNB • LGALS3 • LGALS3BP • TGFB1

Cilengitide sensitivity is predicted by overall integrin expression in breast cancer (AACR 2025) - "We tested an additional pan-ITGAV inhibitor (GLPG0187) to determine how generalizable our findings on cilengitide sensitivity might be to integrin inhibition. Integrin inhibitors are appealing candidates to pursue as anti-cancer drugs because they are generally well-tolerated, but their efficacy is mixed, possibly due to the absence of predictive markers. Cilengitide induces death in breast cancer cells with low integrin abundance, where complementary ECM promotes survival. Thus, integrin inhibition in breast cancer warrants further study."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • FN1 • ITGA3 • ITGA6 • ITGB3 • ITGB4 • ITGB5

Cilengitide sensitivity is predicted by overall integrin expression in breast cancer. (PubMed, Breast Cancer Res) - "Integrin inhibitors are appealing candidates to pursue as anti-cancer drugs because they are generally well-tolerated, but their efficacy is mixed, possibly due to the absence of predictive markers. Cilengitide induces death in breast cancer cells with low integrin abundance, where complementary ECM promotes survival. Thus, integrin inhibition in breast cancer warrants further study."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • FN1 • ITGA3 • ITGA6 • ITGB3 • ITGB4 • ITGB5

Post-exposure suppression of radiation pneumonitis suggests non-redundant independent effects of TGF-beta and TRAIL/DR5 (AACR 2024) - "While some rescue from radiation pneumonitis was observed via GLPG0187, it was to a lesser extent compared to treatment of WT and TRAIL-/- C57Bl/6 mice with TLY012. Future directions include investigating the synergistic effects between TLY012 and GLPG0187 in suppressing radiation pneumonitis and decreasing fibrotic response to radiation."

Oncology • Thoracic Cancer • TGFB1

Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma. (PubMed, Front Immunol) - "Interaction between the Sema7a and Integrin-β1 was detected using the Integrin-β1 blocking antibody (GLPG0187)...Sema7a may play an important role in asthma airway remodeling by inducing EMT. Therefore, new therapeutic approaches for the treatment of chronic asthma, could be aided by the development of agents that target the Sema7a."

Journal • Asthma • Fibrosis • Pulmonary Disease • Respiratory Diseases • SEMA7A • TGFB1

Lineage-Specific Integrin alpha-V Augmentation Promotes Integrin/Akt/mTORC1 Signaling Pathway in Marfan Syndrome Aortic Aneurysm (AHA 2022) - "As biological proof of concept, GLPG0187 treatment in Fbn1C1039G/+ mice decreased aneurysm growth via reduced ITGAV signaling. Mechanistically, blockade of ITGAV leads to diminished Akt and mTORC1 activation. Ultimately reducing aortic SMC proliferation, migration and phenotype modulation, which have all been associated with aortic aneurysm development and growth."

Cardiovascular • Genetic Disorders

Pan-integrin inhibitor GLPG-0187 promotes T-cell killing of mismatch repair-deficient colorectal cancer cells by suppression of SMAD/TGF-β signaling. (PubMed, Am J Cancer Res) - "GLPG-0187 promoted significant immune cell killing of the CRC cells by TALL-104 T lymphoblast cells and reduced phosphoSMAD2 in HCT116 p53-null cells either in the absence or presence of exogenous TGF-β. Our results suggest that TGF-β signaling inhibition by a general integrin receptor inhibitor may boost T-cell killing of MMR-deficient colorectal cancer cells and suggest that a combination of anti-GDF-15 in combination with TGF-β blockade be further investigated in the treatment of MMR-deficient mCRC. Our results support the development of a novel immune-based therapeutic strategy to treat colorectal cancer by targeting the TGF-β signaling pathway through integrin receptor blockade."

Journal • Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CCL20 • CXCL5 • GDF15 • TGFB1

Broad spectrum integrin inhibitor GLPG-0187 bypasses immune evasion in colorectal cancer by TGF-β signaling mediated downregulation of PD-L1. (PubMed, Am J Cancer Res) - "Fluorescently labeled wild-type HCT-116 colorectal cancer cells and TALL-104 T-cells were co-cultured and treated with GLPG-0187, a small molecule integrin inhibitor, at various doses. Probing for additional downstream markers of TGF-β and up-stream markers of PD-L1 will help to further elucidate this mechanism. Further co-culture experiments will also include anti-PD-L1 and anti-PD-1 therapy to investigate the viability of integrin inhibition as an adjuvant to immune checkpoint blockade."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1 • TGFB1

Bypassing immune evasion in colorectal cancer by integrin inhibition-mediated downregulation of PD-L1 (AACR 2023) - "Fluorescently labeled wild-type HCT-116 colorectal cancer cells and TALL-104 T-cells were co-cultured and treated with GLPG0187, a small molecule integrin inhibitor, at various doses. Probing for additional downstream markers of TGFβ and up-stream markers of PD-L1 will help to further elucidate the mechanism. Further co-culture experiments include anti-PD-L1 and anti-PD-1 therapy to investigate the viability of integrin inhibition as an adjuvant to immune checkpoint blockade."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Integrin inhibitor GLPG-0187 promotes T-cell killing of mismatch repair-deficient colorectal cancer cells by suppression of SMAD/TGF-β signaling (AACR 2023) - "However, GLPG-0187 promoted significant immune cell killing of the CRC cells by TALL-104 T lymphoblast cells. Our results suggest that TGF- signaling inhibition by a general integrin receptor inhibitor may boost T-cell killing of MMR-deficient colorectal cancer cells, and suggest that a combination of anti-GDF-15 in combination with TGF- β blockade should be further investigated in the treatment of MMR-deficient mCRC. Our results support the development of a novel immune-based therapeutic strategy to treat colorectal cancer by targeting the TGF-β signaling pathway through integrin receptor blockade."

Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CCL20 • CXCL5 • GDF15 • TGFB1

Lineage-Specific Induced Pluripotent Stem Cell-Derived Smooth Muscle Cell Modeling Predicts Integrin Alpha-V Antagonism Reduces Aortic Root Aneurysm Formation in Marfan Syndrome Mice. (PubMed, Arterioscler Thromb Vasc Biol) - "The integrin αv-FAK-Akt signaling pathway is activated in induced pluripotent stem cell SMCs from MFS patients, specifically from the SHF lineage. Mechanistically, this signaling pathway promotes SMC proliferation and migration in vitro. As biological proof of concept, GLPG0187 treatment slowed aneurysm growth and p-Akt signaling in Fbn1 mice. Integrin αv blockade via GLPG0187 may be a promising therapeutic approach to inhibit MFS aneurysmal growth."

Journal • Preclinical • Cardiovascular • Genetic Disorders