Clonal transcriptomics identifies mechanisms of chemoresistance and empowers rational design of combination therapies.

ABSTRACT: Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained challenging. Here, we utilise clonal transcriptomics with WILD-seq; Wholistic Interrogation of Lineage Dynamics by sequencing, in mouse models of triple-negative breast cancer (TNBC) to understand response and resistance to therapy, including BET bromodomain inhibition and taxane-based chemotherapy. These analyses revealed oxidative stress protection by NRF2 as a major mechanism of taxane resistance and led to the discovery that our tumour models are collaterally sensitive to asparagine deprivation therapy using

SUBMITTER: Wild SA 

PROVIDER: S-EPMC9757829 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature