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 only be solved through multidisciplinary development of preclinical surrogates, models and diagnostic tools that more accurately mimic clinical conditions. Subsequently, the development of patient derived xenograft models in haematological malignancies (in collaboration with Professors Øystein Bruserud and Bjørn Tore Gjertsen), gynecological cancers (in collaboration with Professors Line Bjørge and Camilla Krakstad) and pancreatic cancer (in collaboration with Professor Anders Molven and Dr. Dag Hoem) in Bergen has been performed, in addition to application of multimodal imaging for use in evaluation of novel therapies. The group now has multimodal imaging of over 40 personalized cancer models, spanning most cancer phenotypes in addition to lab-on-a-chip scaffolds for greater in vitro understanding of the bone marrow microenvironments.
• SonoCURE (https://sonocure.w.uib.no/, funding through Norwegian Research Council, NIH and the Regional Health Authorities) 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 modelling. Clinical collaboration with researcher Kotopoulis, Prof. Dimcevski and Prof. Gilja are planned for a Phase II trial follow up from a very successful Phase I trial (Dimcevski et al. J Control Release 2016).
• PreLIM (https://prelim.w.uib.no/, funded by the Norwegian cancer Society and H2020, AML VACCiN) focuses on the development of novel preclinical models of leukemia and lymphomas in the development of novel targeted and immune-therapies (Li et al. Cell Stem Cell 2014), and exploration of microenvironmental factors critical to disease development and emergence of resistant clones.
•Throug the InoVa project (https://inova.w.uib.no/, funded through Helse Vest and the Marie Skłodowska-Curie Innovative training network ISPIC), the group is developing the application of imageguided surgery surgery (Helland et al. PLoS One 2016), whereby fluorescent dyes will target biomarkers on surgically amenable cancers to aid their greater resection. This is particularly relevant to gynecological cancers and sarcomas where the group plans studies in veterinary surgery in dogs in addition to humanized trials.
Recent important results
The SonoCURE team have demonstrated the preclinical development and participated in the clinical application of sonoporation in a world’s first clinical trial in pancreatic ductal adenocarcinoma (J Control Release. 2016 Dec 10;243:172-181). In this study, patients survived on average 17.6 months, compared with 8.9 months through the simple addition of sonoporation to a standard of care treatment protocol.
The PreLIM team contributed to the development of a novel combination of two small molecule inhibitors of JAK and Bcl-2, which synergised in AML.
InoVa purchased the first preclincal system for fluorescence-guided surgery of cancer. This equipment will aid resolution of malignant tissue from normal tissue and should aid the easier visualisation of metastasis, critical in the surgical resection of gynaecological cancers.
Novel bubble delivery systems are being developed within the group which should permit the precise delivery of a drug payload through sonoporation. Furthermore, to aid swift clinical translation, they are developing a number of innovative organoid and immunocompetent patient derived xenograft models to accurately reflect patients pancreatic ductal adenocarcinoma, ovarian carcinoma, leukemia and lymphomas. Evolution of the image-guided surgery system into the treatment of dogs with sarcomas is anticipated in 2018, providing a novel strategy for veterinary oncology care and a unique opportunity to translate observations in companion animals to the clinic.
Current challenges in the field
Development of relevant preclinical models and imaging modalities that will impact the lives of our patients.