Mouse_tumour_growth_supression_by_PARP_and_POLQ_inhibitors_WGS_

Homologous recombination (HR)-deficient tumors are known to be hypersensitive to PARP inhibitor treatment. However, due to their high genomic instability these tumors frequently develop therapy resistance and become unresponsive to treatment. One way to overcome this, may be to suppress error-prone repair processes within cells using inhibitors targeting polymerase ? (POLQ) which is involved in microhomology-mediated end-joining. In line with this it has previously been shown that depletion or inhibition of POLQ is especially toxic for HR-deficient cells. To assess whether POLQ inhibition also suppresses error prone repair processes in vivo, we transplanted HR-deficient organoids in the mammary fat pad of mice and treated the occurring tumors with vehicle, PARP inhibitor, POLQ inhibitor or a combination of both. We observed that especially the combination treatment was successful at suppressing growth of the tumors in vivo. To assess genomic instability and mutational rates in these tumors, genomic DNA was isolated and we would like to perform whole genome sequencing and subsequent mutational signature analysis of the tumors collected from our in vivo study.