MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding
Daniel Massó-Vallés, Marie-Ève Beaulieu, Toni Jauset, Fabio Giuntini, Mariano F. Zacarías Fluck, Laia Foradada, Sandra Martínez-Martín, Erika Serrano, Génesis Martín-Fernández, Sílvia Casacuberta‐Serra, Virginia Castillo Cano, Jastrinjan Kaur, Sergio López‐Estévez, Miguel A. Morcillo, Mohammad Alzrigat, Loay Mahmoud, Antonio Luque-García, Marta Escorihuela, Marta Guzmán, Joaquı́n Arribas, Violeta Serra, Lars‐Gunnar Larsson, Jonathan R. Whitfield, Laura Soucek
Abstract
MYC's role in promoting tumorigenesis is beyond doubt, but its function in the metastatic process is still controversial. Omomyc is a MYC dominant negative that has shown potent antitumor activity in multiple cancer cell lines and mouse models, regardless of their tissue of origin or driver mutations, by impacting on several of the hallmarks of cancer. However, its therapeutic efficacy against metastasis has not been elucidated yet. Here we demonstrate for the first time that MYC inhibition by transgenic Omomyc is efficacious against all breast cancer molecular subtypes, including triple-negative breast cancer, where it displays potent antimetastatic properties both in vitro and in vivo. Importantly, pharmacologic treatment with the recombinantly produced Omomyc miniprotein, recently entering a clinical trial in solid tumors, recapitulates several key features of expression of the Omomyc transgene, confirming its clinical applicability to metastatic breast cancer, including advanced triple-negative breast cancer, a disease in urgent need of better therapeutic options. Significance: While MYC role in metastasis has been long controversial, this manuscript demonstrates that MYC inhibition by either transgenic expression or pharmacologic use of the recombinantly produced Omomyc miniprotein exerts antitumor and antimetastatic activity in breast cancer models in vitro and in vivo, suggesting its clinical applicability.