Epitheliod inflammatory myofibroblastic sarcoma (eIMS) is an aggressive variant of inflammatory myofibroblastic tumour (IMT) that most commonly arises in the abdomen and mediastinum of children, adolescents and young adults. Despite it’s potential to rapidly spread and progress to cause fatality, eIMS has been scarcely studied due to its rarity. This project will utilise unique models and reagents developed in our laboratory to investigate the molecular basis of eIMS, and to test new treatments that could be applied to improve patient outcomes.
Recent studies, including our own, have identified translocations involving genes encoding the kinase ALK and a nuclear pore protein, RANBP2, as the primary oncogenic driver in eIMS tumours. eIMS and other cancers with RANBP2-ALK translocations are effectively treated with drugs that inhibit activity of ALK (ALKi). While the response rate to treatment with ALKi is very high, relapse on ALKi can occur as a result of acquired mutations in the ALK gene. There are currently no known cures for relapsed ALK-driven cancers, including eIMS. New therapeutic approaches, using combination treatment to prevent or treat relapsed disease, are therefore urgently needed.
The objective of this project is to characterise the molecular functions and signalling pathways activated by expression of RANBP2-ALK, to provide further insight to the molecular pathways underpinning eIMS and other cancers driven by these this translocation, and to apply this information to identify new therapeutic targets and alternative treatments for RANBP2-ALK driven cancers. Since there is currently no standard treatment for patients who relapse on ALKi, there will be impetus for rapid translation of the results from this study to clinical treatment of eIMS. The results from this study may also have direct implications in the treatment of cancers driven by other ALK fusions, including subsets of non-small cell lung cancer and non-Hodgkin lymphoma
We welcome enquiries from potential PhD candidates with passion and ambition for a career in medical research.
Prospective students can find information on CMRI scholarship opportunities here: https://www.cmrijeansforgenes.org.au/research/opportunities-for-research-students/cmri-phd-research-award
The opportunity ID for this research opportunity is 3003