New compound boosts treatment for aggressive breast cancer

Although breast cancer survival rates are overall very high, some forms of cancer are more difficult to treat than others. However, a new compound proves highly effective against these types by targeting a protein that makes cancer cells resistant to treatment.

Triple-negative breast cancer is often resistant to treatment. Its name refers to the hormone receptor status that divides breast cancer into different types, and the cells in this type of cancer are called triple-negative because they do not have estrogen receptors, progesterone receptors, or the protein HER2.

Triple-negative breast cancer tumors can be particularly aggressive, and they tend to occur in women with a defective BRCA1 gene.

It is estimated that approximately 12 percent of breast cancers are triple-negative.

New research, which has recently been published in the journal Science Translational Medicine, tests the effect of a novel anticancer agent on treating different types of breast cancer and finds that a new compound - when administered in combination with conventional anticancer drugs - is "highly effective" for treating both triple negative and HER2 positive breast cancers.

As the authors of the new study note, treatment for triple-negative breast cancer has seen little improvement in the past 30 years, so the recent findings are particularly welcome in this context.

The researchers were led by Dr. Delphine Merino, Dr. James Whittle, Dr. François Vaillant, Prof. Jane Visvader, and Prof. Geoff Lindeman, all of whom are from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.

Targeting cancer's 'Achilles' heel'

Dr. Merino and colleagues combined existing anticancer drugs with a new compound called S63845. The uniqueness of the new compound lies in the fact that it targets MCL-1, which is a protein that has previously been shown to be key for the survival of cancer cells.

"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," explains Dr. Whittle. This advantage has been referred to by the researchers as "Achilles' heel."

As the authors explain in the study, MCL-1 is often overexpressed in breast cancer patients, and high expression usually means poor life expectancy for the patient.

In the new research, Dr. Merino and team tested the effect of the MCL-1 inhibitor in cancer cell cultures, as well as in tissue samples taken from breast cancer patients who had high levels of MCL-1.

Dr. Vaillant explains the methodology used, saying, "With the support of the Victorian Cancer Biobank, and samples donated by breast cancer patients, we have generated a large number of laboratory models that mimic how tumors behave and respond to therapy in the patient, allowing us to test a range of anti-cancer drugs."

"In addition, we [...] performed molecular analysis to anticipate the mechanisms of resistance that may occur," Drs. Whittle and Merino told Medical News Today.

'Fantastic hope' for triple negative cancer

S63845 worked together with existing drug docetaxel to combat triple-negative breast cancer, and with the drugs trastuzumab or lapatinib to inhibit HER2-positive breast cancer.

"Combining S63845 with standard therapies, such as chemotherapy or targeted drugs such as Herceptin [trastuzumab], proved highly effective in killing these very aggressive tumor types," says Dr. Merino.

Dr. Whittle also stresses the advantages of combining the new compound with existing treatment.

"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 tumors, so to see a response to the combined therapy in this tumor type is very exciting."

Dr. James Whittle

Referring to the compound's "potent synergistic effect" with chemotherapy, Dr. Whittle and Dr. Merino told Medical News Today that this is "a fantastic hope for patients with triple-negative breast cancer."

Prof. Lindeman also emphasizes the fact that triple-negative breast cancers urgently need alternative forms of treatment. He says, "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."

However, the authors also note the limitations of their study. "[T]hese results are an early indication of effectiveness," said Dr. Whittle and Dr. Merino, "and further work will be required to identify which patients are more likely to respond and what will be the best strategy to adopt in the case of tumor recurrence."

The researchers hope that their study "will provide the momentum for the development of clinical trials in breast cancer patients."