Dostarlimab in the Treatment of Recurrent or Primary Advanced Endometrial Cancer

Kasherman, Lawrence; Ahrari, Soha; Lheureux, Stéphanie

doi:10.2217/fon-2020-0655

Cited by 36 publications

(25 citation statements)

References 57 publications

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“…EC is one of the most common female genital malignant tumours, whose morbidity and mortality are increasing across the world, especially in China [19,20]. The primary reasons for its treatment failure are distant metastasis and local recurrence [21]. Therefore, discovering the molecular mechanisms underlying the cell proliferation and apoptosis of EC will be particularly helpful in providing an experimental basis for the development of valid targeted curative drugs.…”

Section: Discussionmentioning

confidence: 99%

DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells

et al. 2021

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Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated. DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and ow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These ndings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells. Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.

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Section: Discussionmentioning

confidence: 99%

DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells

et al. 2021

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“…Approximately 20–30% of patients with endometrial cancer have MSI-H disease and are eligible for checkpoint inhibitor monotherapy. The GARNET trial (ClinicalTrials.gov NCT02715284 ) demonstrated promising response rates of 42% with dostarlimab (a PD-1 inhibitor) in patients with recurrent or advanced endometrial cancer who had progression during or after platinum-based chemotherapy and had MSI-H tumors [ 30 ].…”

Section: Mechanisms Of Action Of Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immunotherapy-Related Imaging Findings in Patients with Gynecological Malignancies: What Radiologists Need to Know

et al. 2021

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Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune checkpoint inhibitors should be aware of unconventional immune-related imaging features for the evaluation of tumor response and immune-related adverse events. In this paper, immune checkpoint inhibitors used for gynecological malignancies and their mechanisms of action are briefly presented. In the second part, patterns of pseudoprogression are illustrated, and different forms of immune-related adverse events are discussed.

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“…Dostarlimab (also known as TS-042, GSK4057190A, and Jemperli ® ) is a programmed death (PD)-1 receptortargeting humanized IgG4k antibody (49)(50)(51)(52)(53)(54). In April 2021, dostarlimab received accelerated FDA approval based on the data resultant from the GARNET trial (code: NCT02715284), a multicenter, multicohort, open-label trial involving patients with solid tumors in advanced stages (50).…”

Section: Dostarlimabmentioning

confidence: 99%

Monoclonal Antibodies (mAbs) Approved for Cancer Treatment in the 2020s

et al. 2021

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: Monoclonal antibodies are one of the most eminent types of immunotherapeutics that have taken over the biopharmaceutical market because they are approved for a wide range of cancers, either blood-based malignancies or solid tumors, and also non-cancer indications, from migraine to viral infections. Due to their wide applicability as immunotherapeutics, countless biopharmaceutical companies try to be in the competition by developing monoclonal antibodies and advancing into clinical trials with them. Since the approval of the first monoclonal antibodies, the speed of their discovery and approval for medical use have been rather incremental, so that the progress of this market has been anticipated to increase in the current decade. Herein, we take a look at some of the monoclonal antibodies, which have been approved for clinical use in the current decade, so far. Moreover, we underline the encouraging results from the clinical trials that led to the approval of these immunotherapeutics.

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Dostarlimab in the Treatment of Recurrent or Primary Advanced Endometrial Cancer

Cited by 36 publications

References 57 publications

DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells

DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells

Immunotherapy-Related Imaging Findings in Patients with Gynecological Malignancies: What Radiologists Need to Know

Monoclonal Antibodies (mAbs) Approved for Cancer Treatment in the 2020s

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