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Clinical and molecular response to alpha1-oleate treatment in patients with bladder cancer

Haq, Farhan LU ; Sabari, Samudra LU ; Háček, Jaromir ; Brisuda, Antonín ; Ambite, Ines LU orcid ; Cavalera, Michele LU ; Esmaeili, Parisa LU ; Wan, Murphy Lam Yim LU ; Ahmadi, Shahram LU and Babjuk, Marek , et al. (2024) In Cancer Medicine 13(17).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alpha1-oleate complex, cell shedding, cellular uptake, gene expression, non-muscle invasive bladder cancer
in
Cancer Medicine
volume
13
issue
17
article number
e70149
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85203534499
  • pmid:39254154
ISSN
2045-7634
DOI
10.1002/cam4.70149
language
English
LU publication?
yes
id
e3053634-36ba-4008-ac34-0a9ba55f5184
date added to LUP
2024-11-15 11:05:20
date last changed
2025-07-12 07:26:11
@article{e3053634-36ba-4008-ac34-0a9ba55f5184,
  abstract     = {{<p>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.</p>}},
  author       = {{Haq, Farhan and Sabari, Samudra and Háček, Jaromir and Brisuda, Antonín and Ambite, Ines and Cavalera, Michele and Esmaeili, Parisa and Wan, Murphy Lam Yim and Ahmadi, Shahram and Babjuk, Marek and Svanborg, Catharina}},
  issn         = {{2045-7634}},
  keywords     = {{alpha1-oleate complex; cell shedding; cellular uptake; gene expression; non-muscle invasive bladder cancer}},
  language     = {{eng}},
  number       = {{17}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Cancer Medicine}},
  title        = {{Clinical and molecular response to alpha1-oleate treatment in patients with bladder cancer}},
  url          = {{http://dx.doi.org/10.1002/cam4.70149}},
  doi          = {{10.1002/cam4.70149}},
  volume       = {{13}},
  year         = {{2024}},
}