New Breast Cancer Combination Treatment May Help With Gene Mutations

A new breast cancer combination treatment may help patients with certain gene mutations, according to a study published in Molecular Cell.

In the study, the researchers used animal models, organoids, and proteomic screening to investigate treatments for patients who either lack phosphatase and tensin homolog (PTEN) and/or have mutations in the cancer gene phosphoinositide 3-kinase (PI3K).

The researchers observed in the study that the loss of PTEN, which is a gene that suppresses tumors, synergizes with a mutant PI3K gene in forming tumors in mammary glands. Additionally, they found that the loss of PTEN function increased the levels of the glucocorticoid receptor (GR), placing the tumor cells at a higher risk of death.

The gene PTEN has the function of instructing the creation of enzymes in most tissues and functions by inhibiting cell growth and division from being either too rapid or too uncontrollable. Conversely, the enzyme PI3K is able to enhance cell growth and sustain cancer proliferation upon mutation.

Such mutations in PTEN or PI3K is very common among patients with breast cancer, occurring among 50% of patients. Additionally, 10% of patients with breast cancer have combined genetic alterations in PTEN and PI3K.

"These patients could benefit from our findings," said lead author Antonella Papa, PhD, a senior research fellow in biochemistry and molecular biology at Monash Biomedicine Discovery Institute, in a press release. "The finding that GR sensitizes PTEN mutant cells to death is absolutely new; it was the opposite of what you would expect."

Specifically, the researchers found that the combination of a treatment called dexamethasone, which is a currently available anti-inflammatory medication that activates GR, with an AKT inhibitor helped to more effectively suppress the growth of PTEN/PI3K mutant cancer cells than treatment with a single compound.

In order to test the efficacy of this combination therapy, the researchers have begun pre-clinical trials in animal models with plans for conducting clinical trials in the future.

REFERENCE

Monash discoveries suggest new breast cancer treatment. Monash University; October 15, 2020. eurekalert.org/pub_releases/2020-10/mu-mds101520.php. Accessed October 28, 2020.