{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gandhi S"],"funding":["NCATS NIH HHS","NCI","NCI NIH HHS","NIH"],"pagination":["87-95"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7785669"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(1)"],"pubmed_abstract":["Purpose
Increased β-adrenergic receptor (β-AR) signaling has been shown to promote the creation of an immunosuppressive tumor microenvironment (TME). Preclinical studies have shown that abrogation of this signaling pathway, particularly β2-AR, provides a more favorable TME that enhances the activity of anti-PD-1 checkpoint inhibitors. We hypothesize that blocking stress-related immunosuppressive pathways would improve tumor response to immune checkpoint inhibitors in patients. Here, we report the results of dose escalation of a nonselective β-blocker (propranolol) with pembrolizumab in patients with metastatic melanoma.Patients and methods
A 3 + 3 dose escalation study for propranolol twice a day with pembrolizumab (200 mg every 3 weeks) was completed. The primary objective"],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity."],"pmcid":["PMC7785669"],"funding_grant_id":["R01 CA205246","P30CA016056","P30 CA016056","5KL2TR001413-05","UL1TR001412-05","UL1 TR001412","R01CA205246","KL2 TR001413"],"pubmed_authors":["Witkiewicz AK","Bucsek MJ","Repasky EA","Attwood K","Pandey MR","Knudsen ES","Stack S","Wallace PK","Ernstoff MS","Allen C","Tario JD","Mohammadpour H","Gandhi S","Cedeno CD","Funchain P","Ji W","Levis M","Puzanov I","Drabick JJ"],"additional_accession":[]},"is_claimable":false,"name":"Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity.","description":"Purpose
Increased β-adrenergic receptor (β-AR) signaling has been shown to promote the creation of an immunosuppressive tumor microenvironment (TME). Preclinical studies have shown that abrogation of this signaling pathway, particularly β2-AR, provides a more favorable TME that enhances the activity of anti-PD-1 checkpoint inhibitors. We hypothesize that blocking stress-related immunosuppressive pathways would improve tumor response to immune checkpoint inhibitors in patients. Here, we report the results of dose escalation of a nonselective β-blocker (propranolol) with pembrolizumab in patients with metastatic melanoma.Patients and methods
A 3 + 3 dose escalation study for propranolol twice a day with pembrolizumab (200 mg every 3 weeks) was completed. The primary objective","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jan","modification":"2026-04-29T00:00:45.315Z","creation":"2022-02-10T17:25:38.793Z"},"accession":"S-EPMC7785669","cross_references":{"pubmed":["33127652"],"doi":["10.1158/1078-0432.ccr-20-2381","10.1158/1078-0432.CCR-20-2381"]}}