Targeting Cancer’s Achilles’ heel to improve breast cancer treatment

Lead researchers Prof Jane Visvader, Prof Geoff Lindeman, Dr James (Jim) Whittle, Dr Delphine Merino and Dr Francois Vaillant. Image courtesy of WEHI.

Researchers at Walter and Eliza Hall Institute (WEHI) and their collaborators have found a promising new class of anti-cancer agents that targets cancer cells’ Achilles’ heel. The new compound, MCL-1 inhibitor S63845, is one of a promising new class of drugs that triggers tumour cell death.

Combining the new anti-cancer compound S63845 with currently used cancer drugs has been now demonstrated to be more effective in killing triple negative breast cancers and HER2-positive breast cancers, suggesting it should be investigated in clinical trials.

Dr James Whittle at WEHI, who is also a medical oncologist at Peter Mac, said that S63845 targeted MCL-1, a protein that WEHI scientists have previously shown to be important for cancer cell survival.

“MCL-1 gives cancer cells a survival advantage, allowing them to resist chemotherapy or other anti-cancer therapies that would otherwise trigger cancer cell death.”

“Importantly, the combination of the MCL-1 inhibitor S63845 with standard therapies was far more effective than either treatment alone. These can be incredibly aggressive tumours, so to see a response to the combined therapy in this tumour type is very exciting.”

Professor Geoff Lindeman, also a medical oncologist at the Peter Mac and Royal Melbourne Hospital, said MCL-1 inhibitor S63845 was one of a promising new class of drugs.

“Our hope is that it will be possible to combine MCL-1 inhibitors with conventional therapies to more effectively treat certain types of breast cancer and deliver better outcomes for our patients,” Professor Lindeman said.

MCL-1 is a critical anti-cancer therapeutic target. It is found at excessive levels in triple negative and HER2-positive breast cancers, and is often associated with poor outcomes for patients.

Around one in three Australian women with breast cancer have a triple negative or HER2-positive breast cancer. Professor Lindeman said triple negative breast cancers, in particular, were in urgent need of new treatment options.

“Triple negative breast cancers have not seen the same improvement in targeted therapies, or survival, as some other types of breast cancer,” he said.

The study was published today in Science Translational Medicine.

The research was supported by the Australian Cancer Research Foundation amongst others.

The original news post was published on the WEHI website.