Killing 'Sleeper Cells' May Prevent Relapse in ER+ Breast Cancer Therapy

The anti-cancer medicine venetoclax may improve the current therapy for estrogen receptor-positive (ER+) breast cancer, according to preclinical studies.¹

Led by Walter and Eliza Hall Institute researchers, the new study used breast cancer cells taken from patients and demonstrated that venetoclax was effectively able to kill sleeping, or 'senescent,' cancer cells.¹

The results from the study support the efforts of the phase 1 clinical trial in Melbourne, Australia that combines venetoclax with hormone therapy and CDK4/6 inhibitors for treatment of patients with ER+ breast cancer.¹

Since the receptor-positive nature of ER+ breast cancer means that it will grow in response to the female hormone estrogen, current treatment of ER+ breast cancers combines an antihormone therapy, which prevents estrogen signaling, and a CDK4/6 inhibitor drug. These treatments combined force the cancer cells into senescence but does not kill them, leading to a higher likelihood of relapse.¹

However, using hormone ER+ breast cancer samples from patients, the researchers demonstrated that adding venetoclax to the current combination treatment could prolong the cancer's response to treatment by killing the senescent cells.¹

“These promising results provided a justification for starting clinical trials to look at a 'triple therapy' combining venetoclax, hormone therapy and a CDK4/6 inhibitor in patients with ER+ breast cancer,” said Professor Lindeman, MD, a clinician-scientist at the Institute and a medical oncologist at the Peter MacCallum Cancer Centre, in a prepared statement.²

Lindeman explained further that the phase 1 PALVEN trial taking place in Melbourne will look at the safety of the triple therapy combination for patients, as well as patients' tumor response to the treatment.2

ER+ breast cancer is currently the most common form of breast cancer in Australia, at approximately 70% of breast cancer cases in the country.¹

“It would be wonderful to see a new therapy that improves the outcomes of patients with ER+ breast cancer,” Professor Lindeman said.²

REFERENCES

• Whittle JR, Vaillant F, Surgenor E, et al. Dual targeting of CDK4/6 and BCL2 pathways augments tumor response in estrogen receptor positive breast cancer. Clinical Cancer Research. 2020. doi: 10.1158/1078-0432.CCR-19-1872
• Killing 'sleeper cells' may enhance breast cancer therapy [news release]. Walter and Eliza Hall Institute; May 7, 2020. sciencedaily.com/releases/2020/05/200507095608.htm. Accessed on May 18, 2020.