BACKGROUND: The tumoricidal complex alpha1-oleate targets bladder cancer cells, triggering rapid, apoptosis-like tumor cell death. Clinical effects of alpha1-oleate were recently observed in patients with non-muscle invasive bladder cancer (NMIBC), using a randomized, placebo-controlled study protocol. AIMS: To investigate if there are dose-dependent effects of alpha1-oleate. MATERIALS AND METHODS: Here, patients with NMIBC were treated by intravesical instillation of increasing concentrations of alpha1-oleate (1.7, 8.5, or 17 mM) and the treatment response was defined relative to a placebo group. RESULTS: Strong, dose-dependent anti-tumor effects were detected in alpha1-oleate treated patients for a combination of molecular and clinical indicators; a complete or partial response was detected in 88% of tumors treated with 8.5 mM compared to 47% of tumors treated with 1.7 mM of alpha1-oleate. Uptake of alpha1-oleate by the tumor triggered rapid shedding of tumor cells into the urine and cell death by an apoptosis-like mechanism. RNA sequencing of tissue biopsies confirmed the activation of apoptotic cell death and strong inhibition of cancer gene networks, including bladder cancer related genes. Drug-related side effects were not recorded, except for local irritation at the site of instillation. DISCUSSION AND CONCLUSIONS: These dose-dependent anti-tumor effects of alpha1-oleate are promising and support the potential of alpha1-oleate treatment in patients with NMIBC.

• Keywords
• alpha1‐oleate complex, cell shedding, cellular uptake, gene expression, non‐muscle invasive bladder cancer,
• MeSH
• Administration, Intravesical MeSH
• Apoptosis drug effects   MeSH
• Oleic Acid * therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * drug therapy   pathology   genetics   MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase I MeSH
• Clinical Trial, Phase II MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Oleic Acid * MeSH
• Antineoplastic Agents MeSH