Mitigate for Researchers
The scientific community involved in GIST research and related fields will be able to directly utilise the project outcomes to further progress their research and apply the treatment process to other diseases.
The usual scientific procedures for the development of new diagnostic and therapeutic targeted radiopharmaceuticals will be accelerated as a result of the evaluated methods established in MITIGATE. PBPK modelling methods can be applied to other targeted radionuclide therapies, fostering corresponding research for many other substances. The recent developments of understanding GIST resistance beyond development of secondary and tertiary mutations (e.g. dedifferentiation and KIT loss) explain the resistance to imatinib and other drugs. However, this improved understanding cannot be converted to drug therapy approach as it is highly individualised and drugs to be developed might be applied to only very few patients. Our closed loop model can be applied by researchers in related fields to those different concepts of personalised tumour therapy. The proof of concept of targeting TKI-resistant GIST with radiopharmaceuticals in humans will enable new concepts for using this molecular information for the development of novel treatment strategies. The results from biokinetic modelling of human data reveals novel insights for the translation of preclinical data into the human situation, with an impact on general development strategies of novel targeted radiopharmaceuticals. From a broader perspective, improved cooperation between entirely different branches of research is expected as a direct consequence of the development of endoscopic-assisted biopsy and manipulator-assisted seed placement.
In particular, the establishment of refined treatment guidelines for drug resistant GIST will be of relevance to IRDiRC and RARECANCER and it is expected that the research approach and results will be incorporated into the IRDiRC to ensure that developments in rare disease research are shared and resources combined as efficiently as possible. GIST as a molecularly well defined disease acts as the role model for other solid tumours with a much higher incidence rate. Although not an orphan disease, lung cancer consists of several molecularly well-defined subtypes all in the same incidence range as GIST. The lessons learned from GIST will be applied to overcome the problems in other medication-resistant, oligometastatic diseases. The IRDiRC/RareCancer will specifically be impacted by dedicated research in the field of orphan diseases.
MITIGATE targets a problem that will, within a few years, arise from other diseases with short life expectancy. In a similar method, scientists outside the consortium will be able to use MITIGATE results, having been informed through scientific networks, publications and conferences.