Impact of mitochondrial folate metabolism activity on the sensitivity to methotrexate in leukaemia

The transformation from a normal cell to a cancerous one requires metabolic changes to fuel the high metabolic demands of cancer cells. In recent years there have been a number of new discoveries connecting known aberrations in oncogenic and tumour suppressor pathways with metabolic alterations required to sustain cell proliferation and migration. However, an understanding of the selective advantage of these metabolic alterations and their relevance for the treatment of cancer is still lacking. This innovative PhD project aims to discover new therapies targeting the metabolism of blood cancers. The cross-disciplinary project is build upon recent discoveries in cancer metabolism and previous knowledge of the treatment of blood cancers with antifolates (drugs that block the action of folic acid and thereby inhibit proliferation of cancer cells).

The PhD candidate will gain an understanding of genomics, cellular biology, metabolism, pathophysiology and pharmacology in the context of blood cancers. The candidate will learn and apply state-of-the-art metabolomics protocols to interrogate cancer metabolism in in vitro cell culture systems and in vivo mouse models of cancer. The candidate will advance his/her career development towards becoming and independent researcher in the fields of leukaemia biology and/or cancer metabolism.

Keywords: Leukaemia, Acute lymphoblastic leukaemia, One-carbon metabolism, Methotrexate