SP11: Elucidation and therapeutic targeting of vessel co-option as adaptation under anti-angiogenic therapy for metastatic colorectal cancer

Blood vessels are critical for tumor growth and metastasis. Disseminated cancer cells require close proximity to blood to form a solid metastasis mass. This is achieved either by sprouting new branches from capillaries or by co-opting the pre-existing vascular bed. While there are drugs available against sprouting angiogenesis, coopted tumor blood vessels usually become resistant to this treatment.  

Lena Conradi's group has extensive expertise in tumor angiogenesis and has pioneered the characterization of vessel cooption vs. sprouting angiogenesis in liver metastases of colorectal cancer. Andreas Fischer's group studies vascular biology and vascular-controlled organ metabolism.

By joining forces, we will unravel the molecular basis of angiogenic vs. coopted tumor vessels in metastatic colorectal cancer using mouse models, human patient material, cell culture models and in silico analyses. The PhD-candidate of the first cohort (Fischer lab) will perform transcriptomic and metabolomic analyses to compare vascular adaptations in response to tumor and tumor therapy. The first cohort´s MD candidate (Conradi group) will collect human and mouse colorectal cancer and metastasis samples to perform histological analyses. The PhD- (Conradi lab) and MD- (Fischer group) candidates of the second cohort will take advantage of translational organoid and mouse models to identify potential therapeutic targets and perform drug screens.

Through this comprehensive analysis, we aim to identify molecular determinants that drive resistance to angiogenic therapy in colorectal cancer.