Pharmacokinetic analysis of omomyc shows lasting structural integrity and long terminal half-Life in tumor tissue

Marie-Eve Beaulieu, Sandra Martínez-Martín, Jastrinjan Kaur, Virginia Castillo Cano, Daniel Massó Vallés, Laia Foradada Felip, Sergio López-Estévez, Erika Serrano del Pozo, Hugo Thabussot, Laura Soucek

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Resum

MYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reached clinical stage. However, since the in vivo stability of therapeutic proteins, especially within the tumor vicinity, can be affected by proteolytic degradation, the perception of Omomyc as a valid therapeutic agent has been often questioned. In this study, we used a mass spectrometry approach to evaluate the stability of Omomyc in tumor biopsies from murine xenografts following its intravenous administration. Our data strongly support that the integrity of the functional domains of Omomyc (DNA binding and dimerization region) remains preserved in the tumor tissue for at least 72 hours following administration and that the protein shows superior pharmacokinetics in the tumor compartment compared with blood serum.
Idioma originalEnglish
Número d’article826
Nombre de pàgines10
RevistaCancers
Volum15
Número3
DOIs
Estat de la publicacióPublicada - 29 de gen. 2023

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