Periodic Reporting for period 2 - PACA-MET (Genome-wide surveys and functional analysis of pancreatic cancer metastasis drivers)
Período documentado: 2021-05-01 hasta 2022-10-31
First, we developed/improved and extensively validated new computational tools required for cancer genome analyses in mice, the model organism that is critical for PACA-MET (published in Lange et al, Nature protocols 2020; and Mueller et al Nature communications 2020). This was necessary as available pipelines had been originally developed for humans and do not account for species-specific differences in genome structures and experimental settings. These pipelines and protocols are online accessible and are now a gold-standard for mouse cancer genomics.
Second, we developed new tools and methodology for somatic genome engineering and genetic screening in the mouse pancreas (Kaltenbacher et al, Nature protocols 2022; and Braun et al, Nature protocols 2022; Weber et al Nature Reviews Cancer 2020 and unpublished). These universally applicable technologies are not only essential work-horses for the conduction of PACA-MET research, but also promise to be a major driver of scientific discoveries in the field.
Third, we engineered a series of mouse models to study newly discovered metastasis driver genes. These and other biological resources, such as our unique mouse cancer cell culture collections or the various new engineered cellular models are already being extensively requested and used locally, nationally and internationally.
Fourth, our work on metastasis biology (so far largely unpublished) has begun to give fundamental new insights in the precise molecular, cellular and organismal processes in KRAS-driven pancreatic cancer cell dissemination. We also noted that our discoveries are relevant beyond pancreatic cancer in other KRAS-initiated malignancies.