Publications

Therapeutic potential of the new TRIB3-mediated cell autophagy anticancer drug ABTL0812 in endometrial cancer.

Felip I, Moiola CP, Megino-Luque C, Lopez-Gil C, Cabrera S, Solé-Sánchez S, Muñoz-Guardiola P, Megias-Roda E, Pérez-Montoyo H, Alfon J, Yeste-Velasco M, Santacana M, Dolcet X, Reques A, Oaknin A, Rodríguez-Freixinos V, Lizcano JM, Domènech C, Gil-Moreno A, Matias-Guiu X, Colas E, Eritja N.

Published: Gynecol Oncol. 2019 Mar 7

S0090-8258(19)30150-7

Abstract

 

OBJECTIVES:

The PI3K/AKT/mTOR pathway is frequently overactivated in endometrial cancer (EC). We assessed the efficacy of ABTL0812, a novel first-in-class molecule presenting a unique mechanism of action inhibiting this pathway.
 

METHODS:

We investigated the effects of ABTL0812 on proliferation, cell death and modulation of intracellular signaling pathways in a wide panel of endometrioid and non-endometrioid cell lines, an inducible PTEN knock-out murine model, and two patient-derived xenograft murine models of EC. Then, TRIB3 expression was evaluated as potential ABTL0812 pharmacodynamic biomarker in a Phase 1b/2a clinical trial.
 

RESULTS:

ABTL0812 induced an upregulation of TRIB3 expression, resulting in the PI3K/AKT/mTOR axis inhibition and autophagy cell death induction on EC cells but not in healthy endometrial cells. ABTL0812 treatment also impaired PTEN knock-out cells to progress from hyperplasia to cancer. The therapeutic effects of ABTL0812 were demonstrated in vivo. ABTL0812 increased TRIB3 mRNA levels in whole blood samples of eight EC patients, demonstrating that TRIB3 mRNA could be used as a pharmacodynamic biomarker to monitor the ABTL0812 treatment.
 

CONCLUSIONS:

ABTL0812 may represent a novel and highly effective therapeutic agent by inducing TRIB3 expression and autophagy in EC patients, including those with poorer prognosis.

LATEST NEWS

11.03.2024

Press Release

AbilityPharma Announces € 7 Million Financing Round to Advance Development of its Clinical Phase 2b Autophagy Inducer ABTL0812 in Metastatic Pancreatic Cancer + info
02.06.2023

Press Release

Ability Pharmaceuticals announces the presentation of the phase 2a results of ABTL0812 as first-line therapy in patients with lung cancer at the ASCO 2023 Annual Meeting in Chicago + info
14.12.2022

Press Release

AbilityPharma Achieves the 30% of the Estimated Recruitment for their Phase 2b Clinical Trial with ABTL0812 + FOLFIRINOX as a First-Line Therapy Treatment in Advanced Pancreatic Cancer + info
21.11.2022

Press Release

AbilityPharma Obtains 1,5M € of Non-Dilutive Funding from Next Generation EU Funds to Further Study the Anticancer Immunomodulatory Effects of ABTL0812 + info
10.11.2022

Press Release

AbilityPharma will attend LSX investical showcase in London to meet with key investors and venture capital firms + info
02.11.2022

Press Release

ABTL0812 shows potential against glioblastoma brain tumors + info
07.10.2022

Press Release

AbilityPharma Secures 2,2M € of Non-Dilutive Funding from the Ministry of Science & Innovation of the Government of Spain to Accelerate the Clinical Development and Regulatory Path of ABTL0812 + info
07.09.2022

Press Release

Carles Domènech, Executive Chairman & CEO of AbilityPharma, Will Attend ESMO Congress in Paris for a Meeting with some of the most Relevant Key Opinion Leaders (KOLs) in the Treatment of Pancreatic Cancer + info
29.06.2022

Press Release

AbilityPharma Will Attend ESMO World Congress on Gastrointestinal Cancer 2022 in Barcelona + info
© 2012 Ability Pharma / All Rights Reserved / Legal Notice / Privacy Police
NEORG