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This combination therapy is being investigated in a Phase I clinical trial (NCT05968690) for the treatment of advanced melanoma. It combines two repurposed small molecules—naltrexone (an opioid receptor antagonist) and propranolol (a beta-adrenergic blocker)—with the standard-of-care immune checkpoint inhibitors ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The rationale is based on preclinical evidence suggesting that dual blockade of beta-adrenergic and opioid receptors can mitigate stress-related pathways that promote tumor growth and suppress the immune system, thereby potentially enhancing the efficacy of immunotherapy. The study is led by Sarah Weiss and focuses on safety, tolerability, and preliminary efficacy of this multi-targeted approach.
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