Clinical and molecular response to alpha1-oleate treatment in patients with bladder cancer.
alpha1‐oleate complex
cell shedding
cellular uptake
gene expression
non‐muscle invasive bladder cancer
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
Sep 2024
Sep 2024
Historique:
revised:
11
06
2024
received:
29
02
2024
accepted:
14
08
2024
medline:
10
9
2024
pubmed:
10
9
2024
entrez:
10
9
2024
Statut:
ppublish
Résumé
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. To investigate if there are dose-dependent effects of alpha1-oleate. 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. 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. These dose-dependent anti-tumor effects of alpha1-oleate are promising and support the potential of alpha1-oleate treatment in patients with NMIBC.
Sections du résumé
BACKGROUND
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
OBJECTIVE
To investigate if there are dose-dependent effects of alpha1-oleate.
MATERIALS AND METHODS
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
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
CONCLUSIONS
These dose-dependent anti-tumor effects of alpha1-oleate are promising and support the potential of alpha1-oleate treatment in patients with NMIBC.
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70149Subventions
Organisme : Swedish Research Council (Vetenskapsrådet)
Organisme : Swedish Cancer Society (Cancerfonden)
Organisme : Royal Physiographic Society in Lund
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : HAMLET BioPharma AB, Lund, Sweden
Informations de copyright
© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.
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