Finding the key to treating triple-negative breast cancer
What do you do when you’ve found a compound that stops cancer in its tracks, but it’s so unstable that it degrades before it can reach its target?
This is the challenge being embraced by Dr Lisa Pilkington, a brilliant young researcher who is working on finding a treatment for an aggressive form of breast cancer: triple-negative.
Breast Cancer Foundation NZ has awarded Dr Pilkington an $80,000 fellowship for her work.
Dr Pilkington, who has a PhD in chemistry from the University of Auckland and a Masters in Applied Statistics from Oxford University, will build on earlier research into anti-cancer compounds that was funded by a joint Health Research Council/Breast Cancer Foundation partnership grant.
“We found an enzyme – PC-PLC – that promotes the growth of various triple-negative breast cancers. That’s the target,” she says. “Not only did we find the target, we also found a PC-PLC inhibitor, or blocker.
“Unfortunately, the blocker degrades within seconds, so it never reaches the target. We’ve now modified these compounds so that they’re more potent and also have better stability.”
The modified compounds are 40 times more stable than the original blocker - but they still only last about 20 minutes.
“We know how they’re degrading,” says Dr Pilkington. “This project is about putting our knowledge into action to increase the compounds’ stability.”
Currently, there is no immunotherapy treatment available for triple-negative breast cancer patients. Chemotherapy is patients’ only option, and cancer cells generally become resistant over time. By extending the PC-PLC’s stability, Dr Pilkington hopes to move towards more targeted therapies for these patients.
“The PC-PLC enzyme is a lock. Now we are working on finding the key. It’s all about the shape and size of molecules – if the key fits the lock properly, it can stop the enzyme properly.”
She aims to get the blockers into preclinical trials by the end of her two-year project. “That would be the dream.”
Dr Pilkington has a personal connection with the disease. Her aunt is a breast cancer survivor and was treated with Herceptin – a drug developed by researchers like Lisa.