Mesenchymal tumor cells drive adaptive resistance of Trp53^-/- breast tumor cells to inactivated mutant Kras.

ABSTRACT: As precision medicine increases the response rate of treatment, tumors frequently bypass inhibition, and reoccur. In order for treatment to be effective long term, the mechanisms enabling treatment adaptation need to be understood. Here, we report a mouse model that, in the absence of p53 and the presence of oncogenic Kras^G12D , develops breast tumors. Upon inactivation of Kras^G12D , tumors initially regress and enter remission. Subsequently, the majority of tumors adapt to the withdrawal of Kras^G12D expression and return. Kras^G12D -independent tumor cells show a strong mesenchymal profile with active RAS-RAF-MEK-ERK (MAPK/ERK) signaling. Both Kras^G12D -dependent and Kras^G12D -independent tumors display a high level of genom

SUBMITTER: van Weele LJ 

PROVIDER: S-EPMC9441006 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature