From Health to Cancer: Charting the Gut’s Metabolic Shift using Preclinical Mouse Models

The power of genetically engineered mouse models (GEMMs) and organoid models have radically transformed how we study cancers and the way we identify new targets for cancer treatment. These tools have provided us with a controlled environment to better understand the changes in energy production and metabolism that occur in cancer cells as they transform from a normal cell towards a cancerous state.

GEMMs are special mice that have been altered genetically to develop specific types of cancer, allowing us to study the changes in metabolism that occur when cancers form. By using organoid technology, we can grow cancer cells from GEMM mice or human patients in the laboratory that mimics the way they grow in the body, providing insight into how cancer cells interact with their surroundings and how changes in metabolism impact tumour growth and more importantly whether a patient will respond to treatment. While traditional methods to study metabolism lose the spatial information of cells being studied, metabolomic imaging approaches help visualize spatiotemporal metabolomic dynamics of cancer metabolism. My group utilizes GEMMs, organoid models together with novel metabolism mapping techniques to study colon cancers carrying a mutation in the KRAS gene, which are specifically resistant to current therapies. We aim to understand how cancer cells acquire their molecular building material to help them grow, spread to different organs in the body and acquire resistance to therapies.

We have identified new drug targets for treatment that specifically address changes in metabolism of colon cancer cells, leading to the development of new strategies to slow down or in some instances prevent tumour growth. Our aim is to establish new methodologies and approaches to address these questions. This will be through preclinical mouse modelling to reflect the genetic complexity of colorectal cancer, using in vivo gene editing to model cancer development and stepwise progression, performing in vivo genetic screens to find new determinants of cancer formation and mouse colon transplantation models to reflect human disease. As we continue our research in this field, we look forward to discovering even more ways to effectively target and treat this disease. Given the similarities between the different types of cancer, it is easy to envision that learnings and expertise from our work would be of great relevance to the ongoing work in Turku Bioscience and foster more collaborative ties.

Group’s website

Dr. Arafath Najumudeen is a new affiliate of Turku Bioscience. He completed his doctoral thesis under the supervision of Daniel Abankwa at Turku Bioscience and after six years of postdoctoral work at the CRUK Beatson Institute in the UK, he recently returned to Finland after being awarded the Academy of Finland Research Fellowship. He now has his independent laboratory at the Institute of Biotechnology at HiLIFE at the University of Helsinki.