Could ‘Turning Off’ a Key Gene Prevent the Development of Triple-Negative Breast Cancer?
On Tuesday, researchers from the Tulane University School of Medicine announced that they have identified a gene that causes an aggressive form of breast cancer to grow quickly. In addition, they have discovered a way to “turn off” this gene and prevent the cancer from occurring. The conclusions they drew and their research were published in the journal Scientific Reports.
Dr. Reza Izadpanah led the team, which originally looked into two genes and how they play a role in the development of triple negative breast cancer (TNBC).
TNBC accounts for up to 15% of all breast cancers, according to the American Cancer Society. It is considered to be an aggressive cancer because of its rapid growth and it is more likely to spread at the time it’s found. It is also more likely to come back after treatment, compared to other types of breast cancer.
Izadpanah and his colleagues honed in on the TRAF3IP2 gene, which was ultimately proven to suppress the growth and spread of TNBC in mouse models. In experimentation, suppressing the expression of both the TRAF3IP2 and Rab27a genes seemed to lead to a decline in both tumor growth and the spread of the cancer to other organs. However, disabling the TRAF3IP2 gene appeared to show better results – in doing so, the researchers were able to find no spread of the original tumor cells for a full year after treatment.
"Our findings show that both genes play a role in breast cancer growth and metastasis," said Izadpanah. "While targeting Rab27a delays progression of tumor growth, it fails to affect the spread of tiny amounts of cancer cells, or micrometastasis. On the contrary, targeting TRAF3IP2 suppresses tumor growth and spread, and interfering with it both shrinks pre-formed tumors and prevents additional spread. This exciting discovery has revealed that TRAF3IP2 can play a role as a novel therapeutic target in breast cancer treatment."
This is not the only positive news regarding TNBC as of late. During the 2020 ESMO Breast Cancer Virtual Meeting in May, final results from the Phase 2 LOTUS trial were released. The data suggested ipatasertib plus paclitaxel may result in numerically longer overall survival (OS) compared to a placebo plus paclitaxel in patients with TNBC.
Prof. Rebecca Dent of the Division of Medical Oncology, National Cancer Centre Singapore, stated that ipatasertib, which is an oral AKT inhibitor, is under evaluation in cancer with a high prevalence of PI3K/AKT pathway activation.
In the LOTUS trial results, the addition of ipatasertib to first-line paclitaxel appeared to improve the progression-free survival (PFS) in subjects with metastatic TNBC. Patients who were eligible for the study had measurable metastatic TNBC and were previously untreated with systemic therapy. At the final data cut-off, all patients stopped treatment, primarily due to disease progression. In the intent-to-treat group, the median OS was 25.8 months for those receiving ipatasertib plus paclitaxel. This is compared to the 16.9-month average for the placebo plus paclitaxel group.
Suzette Delaloge of the Gustave Roussy in Villejuif, France, who addressed the trial findings, believes that the AKT inhibition in combination with paclitaxel should progress to Phase 3 development for advanced TNBC. This is because the efficacy may not only be limited to PIK3CA/AKT altered tumors.
In the future, some trials may look into the extensive genomical definition of tumors. However, this approach and strategy has yet to be developed.