Tailoring therapies for people with treatment resistant CLL
Chronic lymphocytic leukaemia (CLL) is a blood cancer that in some patients fails to respond to standard treatment. This type of treatment resistance is usually caused by loss of proteins ATM or p53 that would recognise and eliminate cells that are treated successfully. Recent advances in treatment options pose a dilemma for the clinician in deciding which drug is best to use for these patients. It can be appreciated that some drugs allow tumour cells with the loss of ATM or p53 protein to preferentially survive, which is undesirable. Therefore, the right choice of therapy that will not allow ATM and TP53 defective cells to survive is absolutely essential.
We will analyse tumour material from patients on clinical trials in order to examine the behaviour of blood cancers with defective ATM and TP53 cells. We will test in the laboratory individual patients’ cells to determine which currently available treatment is most efficient in eliminating these cells. In addition, we will also investigate some novel therapeutic approaches that work differently from standard drugs. In particular, we will test novel approaches that selectively kill these cells by exacerbating a specific weakness, so called replication stress, a recently described feature of tumour cells.