FULLY FUNDED PHD: Exploiting the role of individual members of the FOXO transcription factor family: do they differentially regulate CLL survival, proliferation and chemosensitivity?

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Chronic lymphocytic leukaemia (CLL) is the most common blood cancer, with ~3,700 new UK diagnoses/year, and remains incurable.

Although the majority of patients initially respond to treatment, all eventually relapse due to the re-emergence of leukaemic cells.

There is a critical need to develop novel treatments for CLL patients and establish biomarkers that enable discrimination between treatment-responsive and non-responsive CLL patients.

CLL cells interact with the tumour microenvironment, which provides survival and growth prompts to leukaemic cells, resulting in disease progression.

Healthy cells have checkpoints that prevent over-expansion of cells, however these checkpoints are disrupted in cancer cells. The forkhead box, class O (FOXO) protein family can behave like brakes, regulating processes responsible for cell cycle arrest and promoting apoptosis.

Indeed, we demonstrated that FOXO1 is inactivated in CLL cells within the tumour microenvironment, resulting in a reduction of the FOXO function. Furthermore, drug treatment can re-activate FOXO1 and induce CLL cell death.

However, studies reveal that FOXO family members behave as tumour promoters in certain cellular contexts.

Therefore this studentship will elucidate the molecular mechanisms that regulate individual FOXO family members, providing fundamental information regarding their regulation in CLL cells, and potentially highlight novel therapeutic avenues.