Mutation Pattern Similarity broadens potential of existing Therapies

Scientists at Queen’s University Belfast and the University of Birmingham have revealed that tumours normally found in blood cancers with mutations in the SF3B1 gene, are capable of responding to some existing PARP inhibitors, a type of drug used to treat cancers which carry similar mutations in the BRCA1 and BRCA2 genes.

Dr Kienan Savage, lead author and Reader at the Patrick G Johnson Centre for Cancer Research at Queen’s, said: “Our findings have clinical implications for the treatment of many cancers. We specifically focused on this genetic mutation as it is found in several difficult to treat leukaemias and other cancers and it affects so many cancer patients. By deepening our understanding of this gene mutation, we have identified new ways of treating these cancers that could improve survival rates.” 

The SF3B1 mutation were sensitive to olaparib, the most common PARP inhibitor, some specific chemotherapies and to radiotherapy. The scientists believe that the SF3B1 mutation disrupts the cell’s ability to make DNA repair proteins, leaving it vulnerable to drugs which target these proteins.   

The SF3B1 mutation occurs in up to 30% of blood cancers called myelodysplastic syndromes, where blood cells don’t form properly. They are difficult to treat as they occur predominantly in older patients who may not be considered fit for treatment. The mutation is also common among uveal melanoma or cancers of the eye, which currently have limited treatment options.  

Dr Katrina Lappin, from Queen’s and first author of the study, added: “Our research shows that cancers with these specific mutations, may be treated effectively with PARP inhibitor therapy drugs, which are less toxic, better at killing cancer cells with these mutations and can be taken at home in tablet form. This could have huge implications for improving outcomes and quality of life of people with these cancers.” 

The researchers now want to test PARP inhibitors in clinical trials with patients who have the SF3B1 mutation to see if they can stop their cancer from spreading.  

Co-author Professor Grant Stewart, of the University of Birmingham, said: “Our work demonstrates that a molecular understanding of how a specific gene mutation affects a cancer cell’s ability to repair damaged DNA can be exploited clinically to specifically tailor the anti-cancer therapy used to treat an individual’s tumour. This will increase the effectiveness of the therapy and hopefully, reduce the chances of re-occurrence.” 

The research was funded by the UK Medical Research Council, Cancer Research UK, Blood Cancer UK, Leukaemia and Lymphoma NI and Great Ormond Street Hospital Children's Charity. 

 'Cancer-associated SF3B1 mutations confer a BRCA-like cellular phenotype and synthetic lethality to PARP inhibitors' published in Cancer Research, (American Association for Cancer Research).

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