Abstract
Rheumatoid arthritis is an untreatable autoimmune disorder. The disease is accompanied
by joint impairment and anomalies, which negatively affect the patient’s quality of life and
contribute to a decline in manpower. To diagnose and treat rheumatoid arthritis, it is crucial to understand
the abnormal signaling pathways that contribute to the disease. This understanding will
help develop new rheumatoid arthritis-related intervention targets. Over the last few decades, researchers
have given more attention to rheumatoid arthritis. The current review seeks to provide a
detailed summary of rheumatoid arthritis, highlighting the basic description of the disease, past occurrences,
the study of epidemiology, risk elements, and the process of disease progression, as
well as the key scientific development of the disease condition and multiple signaling pathways
and enumerating the most current advancements in discovering new rheumatoid arthritis signaling
pathways and rheumatoid arthritis inhibitors. This review emphasizes the anti-rheumatoid effects
of these inhibitors [for the Wnt/β-catenin, Phosphoinositide 3-Kinases (PI3K/AKT), Spleen Tyrosine
Kinase (SYK), and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) signaling
pathways], illustrating their mechanism of action through a literature search, current therapies,
and novel drugs under pre-clinical and clinical trials.
Keywords:
Rheumatoid arthritis, Wnt/β-catenin, phosphoinositide 3- kinases (PI3K/AKT), spleen tyrosine kinase (SYK), granulocyte- macrophage colony stimulating factor (GM-CSF), autoimmune disorder, novel targets, inflammation.
Graphical Abstract
[3]
Silman AJ, Pearson JE. epidemiology 2020; 265-72.
[65]
R. VV. Efficacy and safety of MK-8457, a novel SYK inhibitor for the treatment of rheumatoid arthritis in two randomized, controlled, phase 2 studies. Arthritis Rheumatol 2014; 66: S673-4.
[76]
Sun K, Luo J, Guo J, Yao X, Jing X, Guo F. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: A narrative review. Osteoarthritis Cartilage 2020; 28(4): 400-9.
[78]
Chen CY, Chen J, He L, Stiles BL. PTEN: Tumor Suppressor and Metabolic Regulator. Front Endocrinol 2018; 9: 338.
[80]
Sathe A, Nawroth R. Targeting the PI3K/AKT/mTOR pathway in bladder cancer. In: Methods in molecular biology. Methods Mol Biol 2018; 335-50.
[95]
Kamson DO, Khela HS, Laterra J. Investigational new drugs against glioblastoma. In: Paulmurugan R, Massoud TF, Eds. Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies. Academic Press 2021; pp. 31-77.
[133]
Kivitz A, Hazan L, Hoffman K, Wallin BA. FRI0209 MORAb-022, an anti-granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody (MAB): Results of the first study in patients with mild-to-moderate rheumatoid arthritis. Ann Rheum Dis 2016; 75: 507-7.
[137]
Buckley C, Campos JS, Zhdan V, Becker B, Chauhan D, Davy K, et al. OP0228 GSK3196165 An investigational anti-gm-csf monoclonal antibody, improves patient reported outcomes in a phase iib study of patients with rheumatoid arthritis. Ann Rheum Dis 2019; 78(2): 191-1.
[143]
Kargbo RB. PROTAC-mediated degradation of janus kinase as a therapeutic strategy for cancer and rheumatoid arthritis. ACS Med Chem Lett 2021; 12(6): 945-6.
[144]
Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: An overview of biomedical applications. J Control Release 2012; 161(2): 505-22.