Professor Emmet McCormack is PI of the research group Translational Molecular Imaging in Cancer. Main motivation of the group is the development and effective translation of novel therapies and imaging strategies for the treatment of cancer, particularly cancers with limited therapeutic options.
It is the group’s belief that the current dogma of rushing novel pharmaceuticals through inappropriate preclinical models is one of the major reasons for their limited clinical penetration. This can be solved through multidisciplinary development of preclinical surrogates, models and diagnostic tools that more accurately mimic clinical conditions. Subsequently, the group has led the development of patient derived xenograft models and multimodal imaging for use in the evaluation of novel therapies. Also, lab-on-a-chip scaffolds for greater in vitro understanding of the bone marrow microenvironments have been established.
SonoCURE explores the application of Sonoporation, the transient formation of pores in cells by microbubbles activated by ultrasound, in the treatment of Pancreatic Ductal AdenoCarcinoma (PDAC). The application aims to preclinically elucidate, evaluate, and potentiate a new era of sonoporation theranostics for PDAC through application of innovative biomarker mining, organoid models and preclinical modeling. Phase II trials are planned, following a very successful phase I trial.
PreLIM focuses on the development of novel preclinical models of leukemias and lymphomas in the development of novel targeted and immune therapies, and exploration of microenvironmental factors critical to disease development and emergence of resistant clones.
Finally, the INOvA project is developing the application of image-guided surgery, whereby fluorescent dyes will target biomarkers on surgically amenable cancers to aid their greater resection. This is particularly relevant to gynecological cancers and sarcomas for which trials are planned.
The SonoCURE group has demonstrated that sonoporation with gas filled microbubbles impacts the intracellular signaling of cancer cells and identified biomarkers that can be exploited for therapeutic intervention in combination with sonoporation (Haugse et al. Pharmaceutics 2019). In addition, Ragnhild Haugse and Tormod Karlsen Bjånes will defend their thesis in 2020.
The PreLIM group has identified that stabilization of β-catenin upon B-cell receptor signaling promotes NF-kB target genes transcription in mantle cell lymphoma (Baran-Marszak et al. Oncogene, in press). Furthermore, the group has identified novel smallmolecule therapeutic targets in mantle cell lymphoma (Gelebart et al. submitted 2019) and initiated collaboration with the Moffitt Cancer Center in the development of several novel cell-based immunotherapeutics. Sahba Shafiee successfully defended her thesis on “Translational Development of Preclinical Models and Therapies in Myelodysplastic Syndromes (MDS).”
INOvA purchased the first preclinical system for Fluorescence Image-Guided Surgery (FIGS) in Scandinavia. This equipment will aid resolution and easier visualization of metastasis, critical in the surgical resection of gynecological cancers. Two manuscripts are under revision (Kleinmanns et al.) following the identification of a novel biomarker overexpressed in approximately 90% of ovarian cancer patients. Two further manuscripts are under review describing the immunogram of ovarian cancer patients by mass cytometry. Katharina Bischof and Katrin Kleinmanns successfully defended their PhD theses in 2019, while Shamundeeswari Anandan and Elvira García de Jalón will defend in 2020.
The McCormack group will work to consolidate the different subprojects into one multifaceted research group working at the interface of clinical and basic research. They will endeavor to generate novel immunotherapies based on the biomarkers elucidated through CCBIO and evolve their preclinical modeling platforms to provide state of the art models that impact clinical development of tomorrow’s therapeutics.
Current challenges in the field
The major challenge in the group’s research area is the relevance and penetrance of the model systems employed for translational research. The advent of immunotherapy and the evolving understanding of the tumor microenvironment has dramatically impacted the way we develop and perform preclinical research.