Development of OXY111A, a novel hypoxia-modifier as a potential antitumor agent in patients with hepato-pancreato-biliary neoplasms - Protocol of a first Ib/IIa clinical trial.

Date publication

octobre 2016

Journal

BMC cancer

Auteurs

Membres identifiés du Cancéropôle Est :
Pr LEHN Jean-Marie

Tous les auteurs :
Limani P, Linecker M, Kron P, Samaras P, Pestalozzi B, Stupp R, Jetter A, Dutkowski P, Müllhaupt B, Schlegel A, Nicolau C, Lehn JM, Petrowsky H, Humar B, Graf R, Clavien PA

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/27756258

Résumé

Solid tumors, such as hepato-pancreato-biliary cancer, develop tumor hypoxia with tumor growth. Despite advances in surgery, a majority of these patients are in an unresectable condition. At this stage standard cytotoxic chemotherapy regimens are applied with limited success. Novel biological treatment options based on an antiangiogenic mechanism of action neglect other hypoxia mediated mechanisms (e.g. epithelial-mesenchymal transition, Warburg effect, and immunological response) leading to an increased invasiveness with a poor outcome. The novel antihypoxic molecule myo-inositoltrispyrophosphate (ITPP, OXY111A) acts as an allosteric effector of hemoglobin and promotes normoxia in hypoxic tumors. In preclinical studies, tumor growth was reduced and survival prolonged. Additionally, a beneficial side effect profile was observed.

Référence

BMC Cancer. 2016 Oct;16(1):812