Reawakening the ‘Guardian of the Genome’ to Fight Drug Resistance

• Project description: Dr Neil Portman and his team are identifying new treatment options for CDK4/6 inhibitor resistant (CDKR) breast cancer.
• Why this worked is needed: By pre-empting the resistance of breast cancers to CDK4/6 inhibitors, Dr Portman and his team will gain insights into new treatment alternatives to effectively manage the inevitable resistance of metastatic and advanced breast cancers to these drugs.
• Expected outcomes: The project will help to pinpoint which single or combination therapy might be best for reducing tumour growth in CDKR breast cancer, leading to more effective treatment options for CDKR breast cancer.

Project details
A new class of drug called CDK4/6 inhibitors are poised to become the standard of care for the treatment of advanced and metastatic breast cancer. This will help to significantly improve survival times. Unfortunately, resistance to CDK4/6 inhibitors is already emerging in the clinic, presenting the next major hurdle in achieving zero deaths from breast cancer.

A new NBCF-funded project led by Dr Neil Portman will investigate alternative treatment options for CDK4/6 inhibitor resistant (CDKR) breast cancer. He believes that a factor known as p53 could be essential in the fight against drug resistance. P53 is also known as the ‘Guardian of the Genome’, as it helps combat the development and growth of cancer cells. A class of drugs called MDM2 inhibitors can increase the activity of p53. This may provide a new treatment option for CDKR disease.

Dr Portman and his team have completed preliminary work showing that activation of the p53 factor can treat CDKR tumours. The next step is to test a series of MDM2 drugs, to identify which single or combination therapy is most effective at reducing tumour growth. It is hoped that the findings of this important study will then lead to better treatment options for CDKR breast cancer in the future.