Development of inhibitors of PC-PLC as anticancer therapeutics

Project Objective
Many patients with metastatic breast cancer do not respond to conventional chemotherapy and better strategies to treat these patients are urgently needed. An enzyme called phosphatidylcholine-specific phospholipase C (PC-PLC) is involved in allowing breast cancer cells to grow and invade other tissues. This project seeks to prepare potent and selective drugs that target PC-PLC in breast cancer. We will prepare and examine the effectiveness of these drugs in reducing cancer cell growth, with the aim of providing new treatment options for patients with triple negative breast cancer.

Outcome
This project successfully prepared the most potent and selective drugs that target PC-PLC in breast cancer including a response of 30% greater than the current standard, however it was not stable in-vivo and did not as a result reach the enzyme target in cells limiting their activity against tumours. Work is now underway on a new compound which does not include the structure believed to be causing the instability in vivo, therefore continuing the drive to find new treatment options for patients with triple negative breast cancer.

FIRST NAMED INVESTIGATOR: Associate Professor David Barker
HOST INVESTIGATOR: University of Auckland