The JAK/STAT signaling pathway: from bench to clinic

Hu, Xiaofan; Li, Jing; Fu, Maorong; Zhao, Xia; Wang, Wei

doi:10.1038/s41392-021-00791-1

Cited by 782 publications

(676 citation statements)

References 569 publications

Supporting

Mentioning

623

Contrasting

Unclassified

Order By: Relevance

“…After docking, STAT proteins also get phosphorylated by JAKs leading to their dissociation and dimerization. The activated STAT dimers then translocate to the nucleus and take part in the regulation of transcription [6]. This process can be selectively blocked by small molecule JAK inhibitors [7].…”

Section: Introductionmentioning

confidence: 99%

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients

Tóth

Juhász

Szabó

et al. 2022

IJMS

View full text Add to dashboard Cite

Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.

show abstract

Section: Introductionmentioning

confidence: 99%

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients

Tóth

Juhász

Szabó

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Baricitinib (Olumiant), from Eli Lilly, is an orally active selective inhibitor of JAK1/JAK2 kinases, approved for the treatment of rheumatoid arthritis due to its ability to regulate the inflammatory immune response [58]. In combination with remdesivir, it has been approved for emergency use in advanced stages of COVID-19.…”

Section: Inhibitors Of the Jak-stat Signaling Pathwaymentioning

confidence: 99%

Approaches to the Potential Therapy of COVID-19: A General Overview from the Medicinal Chemistry Perspective

Menéndez

2022

Molecules

View full text Add to dashboard Cite

In spite of advances in vaccination, control of the COVID-19 pandemic will require the use of pharmacological treatments against SARS-CoV2. Their development needs to consider the existence of two phases in the disease, namely the viral infection and the inflammatory stages. The main targets for antiviral therapeutic intervention are: (a) viral proteins, including the spike (S) protein characteristic of the viral cover and the viral proteases in charge of processing the polyprotein arising from viral genome translation; (b) host proteins, such as those involved in the processes related to viral entry into the host cell and the release of the viral genome inside the cell, the elongation factor eEF1A and importins. The use of antivirals targeted at host proteins is less developed but it has the potential advantage of not being affected by mutations in the genome of the virus and therefore being active against all its variants. Regarding drugs that address the hyperinflammatory phase of the disease triggered by the so-called cytokine storm, the following strategies are particularly relevant: (a) drugs targeting JAK kinases; (b) sphingosine kinase 2 inhibitors; (c) antibodies against interleukin 6 or its receptor; (d) use of the traditional anti-inflammatory corticosteroids.

show abstract

“…Hyperstimulation of this pathway has also been found in other cancers, including breast, gastric, lung, prostate, and hematopoietic malignancies [ 35 , 36 , 37 ]. JAK/STAT pathway-mediated tumor progression is mainly due to the expression of a variety of proteins and cytokines involved in cellular proliferation, stemness and self-renewal, survival, and evasion of antitumor immunity [ 37 , 38 ]. Studies have found that more than 50 cytokines and growth factors are responsible for this pathway initiating hematopoiesis, inflammation, and immune suppression in the tumor microenvironment [ 38 ].…”

Section: Targeting Numerous Signaling Pathways Of Ovarian Cancermentioning

confidence: 99%

“…JAK/STAT pathway-mediated tumor progression is mainly due to the expression of a variety of proteins and cytokines involved in cellular proliferation, stemness and self-renewal, survival, and evasion of antitumor immunity [ 37 , 38 ]. Studies have found that more than 50 cytokines and growth factors are responsible for this pathway initiating hematopoiesis, inflammation, and immune suppression in the tumor microenvironment [ 38 ]. STAT is a key driver of immunosuppression through triggering the production of immune checkpoint genes (e.g., PD1, PD-L1, PD-L2, and CTLA-4) [ 39 ], promoting radio- and/or chemoresistance and the failure of targeted immunotherapies [ 22 ].…”

Section: Targeting Numerous Signaling Pathways Of Ovarian Cancermentioning

confidence: 99%

Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements

Akter

Rahman

Hasan³

et al. 2022

Cells

View full text Add to dashboard Cite

Aggressive and recurrent gynecological cancers are associated with worse prognosis and a lack of effective therapeutic response. Ovarian cancer (OC) patients are often diagnosed in advanced stages, when drug resistance, angiogenesis, relapse, and metastasis impact survival outcomes. Currently, surgical debulking, radiotherapy, and/or chemotherapy remain the mainstream treatment modalities; however, patients suffer unwanted side effects and drug resistance in the absence of targeted therapies. Hence, it is urgent to decipher the complex disease biology and identify potential biomarkers, which could greatly contribute to making an early diagnosis or predicting the response to specific therapies. This review aims to critically discuss the current therapeutic strategies for OC, novel drug-delivery systems, and potential biomarkers in the context of genetics and molecular research. It emphasizes how the understanding of disease biology is related to the advancement of technology, enabling the exploration of novel biomarkers that may be able to provide more accurate diagnosis and prognosis, which would effectively translate into targeted therapies, ultimately improving patients’ overall survival and quality of life.

show abstract

The JAK/STAT signaling pathway: from bench to clinic

Cited by 782 publications

References 569 publications

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients

Approaches to the Potential Therapy of COVID-19: A General Overview from the Medicinal Chemistry Perspective

Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements

Contact Info

Product

Resources

About