Targeting 'Achilles' heel' could supercharge breast cancer treatment

August 2, 2017
A new class of anti-cancer agents that target cancer cells' 'Achilles' heel' could help to supercharge breast cancer treatment, improving outcomes for some of the most aggressive types of breast cancer.A research team from the Walter and Eliza Hall Institute in Melbourne, Australia, found that combining anti-cancer compound S63845 with currently used cancer drugs was more effective in killing triple negative breast cancers and HER2-positive breast cancers.L-R: Dr François Vaillant, Dr James Whittle and Dr Delphine Merino Credit: Walter and Eliza Hall Institute

A new class of anti-cancer agents that target cancer cells' 'Achilles' heel' could help to supercharge breast cancer treatment, improving outcomes for some of the most aggressive types of breast cancer.

Combining anti-cancer compound S63845 with currently used cancer drugs was more effective in killing triple negative cancers and HER2-positive breast cancers. This is the first time the S63845 compound, developed by pharmaceutical company Servier, has been shown to be effective for treating , with the promising results suggesting it should be investigated in clinical trials.

The results are particularly important for triple negative breast cancers because, unlike other breast cancers, they have not seen substantial improvements in treatment or patient outcomes in the past 30 years.

The research was led by Dr Delphine Merino, Dr James Whittle, Dr François Vaillant, Professor Jane Visvader and Professor Geoff Lindeman from Melbourne's Walter and Eliza Hall Institute, in collaboration with Servier. The study was published today in Science Translational Medicine.

Professor 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 that triggers tumour cell death by targeting the cancer's 'Achilles' heel'. "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.

Around one in three Australian women with breast cancer have a triple negative or HER2-positive breast cancer. Triple negative breast cancers are particularly common in women with a faulty BRCA1 gene.

Dr Merino said S63845 was particularly effective in treating triple negative and HER-2 positive breast cancers, when tested in samples taken from patients' tumours. "Combining S63845 with standard therapies, such as chemotherapy or targeted drugs such as Herceptin, proved highly effective in killing these very aggressive tumour types," Dr Merino said.

Dr Whittle, who is also a medical oncologist at Peter Mac, said S63845 targeted MCL-1, a protein that Institute scientists had 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," Dr Whittle said.

"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 in this tumour type is very exciting."

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.

A new class of anti-cancer agents that target cancer cells' 'Achilles' heel' could help to supercharge breast cancer treatment, improving outcomes for some of the most aggressive types of breast cancer.A research team from the Walter and Eliza Hall Institute in Melbourne, Australia, found that combining anti-cancer compound S63845 with currently used cancer drugs was more effective in killing triple negative breast cancers and HER2-positive breast cancers. L-R: Professor Jane Visvader, Professor Geoff Lindeman, Dr James Whittle, Dr Delphine Merino and Dr François Vaillant Credit: Walter and Eliza Hall Institute

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.

Dr Vaillant said patient-derived tumours provided a valuable way of studying new breast cancer drugs.

"With the support of the Victorian Cancer Biobank, and samples donated by , we have generated a large number of laboratory models that mimic how tumours behave and respond to therapy in the patient, allowing us to test a range of anti- drugs. This approach can help fast-track the development and transfer of promising drugs to the clinic," Dr Vaillant said.

Explore further: New treatment hope for women with BRCA1 breast cancers

More information: D. Merino el al., "Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer," Science Translational Medicine (2017). stm.sciencemag.org/lookup/doi/ … scitranslmed.aam7049

Related Stories

New treatment hope for women with BRCA1 breast cancers

June 7, 2017
Researchers have found a new way to use immunotherapy, a breakthrough mode of cancer treatment which harnesses the patient's immune system, to treat an aggressive form of breast cancer.

Even low-androgen triple-negative breast cancer responds to anti-androgen therapy

February 24, 2015
A University of Colorado Cancer Center study published today in the journal Molecular Cancer Therapeutics shows that only about 1 percent of triple-negative breast cancer cells in a tumor must be "androgen-receptor-positive" ...

Promising findings towards targeted breast cancer therapy

November 14, 2016
New research led by Conway Fellow, Professor Joe Duffy and Professor John Crown in St Vincent's University Hospital has reported for the first time on a new treatment that could be used in the majority of patients with triple ...

Discovery of potential treatment for aggressive form of breast cancer

November 2, 2016
A new drug could be used to treat one of the most aggressive forms of breast cancer, a research centre based at University College Dublin and St Vincent's Hospital has discovered.

New agents show promise for treating aggressive breast cancers

July 18, 2011
Some of the most aggressive forms of breast cancer are more vulnerable to chemotherapy when it is combined with a new class of anti-cancer agent, researchers from the Walter and Eliza Hall Institute have shown.

New anti-cancer compound shows promise for breast cancer

July 8, 2013
Melbourne researchers have discovered that anti-cancer compounds currently in clinical trials for some types of leukaemia could offer hope for treating the most common type of breast cancer.

Recommended for you

Many pelvic tumors in women may have common origin—fallopian tubes

October 17, 2017
Most—and possibly all—ovarian cancers start, not in ovaries, but instead in the fallopian tubes attached to them.

New bowel cancer drug target discovered

October 17, 2017
Researchers at the Francis Crick Institute have discovered a new drug target for bowel cancer that is specific to tumour cells and therefore less toxic than conventional therapies.

Researchers find novel mechanism of resistance to anti-cancer drugs

October 17, 2017
The targeted anti-cancer therapies cetuximab and panitumumab are mainstays of treatment for advanced colorectal cancer, the second leading cause of cancer-related deaths in the United States. However, many patients have tumors ...

Using artificial intelligence to improve early breast cancer detection

October 17, 2017
Every year 40,000 women die from breast cancer in the U.S. alone. When cancers are found early, they can often be cured. Mammograms are the best test available, but they're still imperfect and often result in false positive ...

New assay may boost targeted treatment of non-Hodgkin lymphoma

October 17, 2017
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer and the most frequently diagnosed non-Hodgkin lymphoma worldwide (nearly 40% of cases). Recent advancements indicate that both the prognosis and choice of treatment ...

Biology of childhood brain tumor subtypes offers clues to precision treatments

October 17, 2017
Researchers investigating pediatric low-grade gliomas (PLGG), the most common type of brain tumor in children, have discovered key biological differences in how mutated genes combine with other genes to drive this childhood ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.