Three-negative new therapy for breast cancer - BBOX1 inhibitor.

Triple-negative breast cancer (TNBC) is known for estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptors 2 (HER2), which account for only 15%-20% of all breast cancers, but are the deadliest of them, with a five-year survival rate of 77% and other types of breast cancer with a five-year survival rate of 93%.
unlike other hormone receptor or HER2-positive cancers, triple-negative breast cancer has almost no targeted therapy available and patients can only rely on surgery, chemotherapy and radiotherapy for treatment, which are less effective than targeted treatments and harm healthy tissue. On July 20,
, in a new study published in the journal Cancer Discovery, Dr. Zhang Qing of the University of Texas Southwestern Medical Center (UTSW) found that BBOX1 could be a viable target for three-negative breast cancer.
this may offer hope for some patients who lack effective treatment options and often face poor prognosis.

Photo Source: Dr. Cancer Discovery Zhang Qing is an Associate Professor in the Department of Pathology at UTSW.
to find a viable drug target for triple-negative breast cancer, his team focused on alpha-oxoglutarate (2-oxoglutarate, 2OG)-dependent enzymes, a family of enzymes containing 70 enzymes, some of which act as oxygen sensors in cells.
to determine the role of these enzymes in triple-negative breast cancer, the researchers used a small pool of interfering RNA (genetic fragments that close the expression of specific genes) to shut down each member of the alpha-ketone diacid-dependent enzyme family in the breast cell lines of different triple-negative breast cancers and healthy people.
research quickly narrows to a specific enzyme, BBOX1, which promotes cell synthesis of carnitine, which plays a key role in energy metabolism.
when the gene responsible for producing BBOX1 is turned off, there is no effect on healthy breast cells, but triple-negative breast cancer cells stop dividing and eventually die.

. BBOX1 promotes the growth of triple-negative breast cancer cells in an enzyme-dependent manner (Photo: Cancer Discovery) At the same time, overexpression of the codeD BBOX1 gene leads to a large proliferation of triple-negative breast cancer cell strains. further research
showed that it was not carnitine (the end product of The BBOX1 enzyme) that caused this effect.
BBOX1 itself seems to be the key to the survival and growth of triple-negative breast cancer cells.
to study how BBOX1 works, the researchers looked at which proteins BBOX1 interacts with in cells.
experimental results show that BBOX1 can be combined with a protein IP3R3, previous studies have shown that IP3R3 is associated with other malignant tumors.
IP3R3 is important in helping mitochondria get energy from sugar.
BBOX1 binds to IP3R3 and prevents it from dedegrading, providing the energy needed to grow three negative breast cancer cells.

. BBOX1 interacts with IP3R3 and regulates the stability of IP3R3 (Photo Source: Cancer Discovery) On the other hand, clearing BBOX1 may prevent the development of triple-negative breast cancer tumors, a conclusion demonstrated in mouse experiments.
injected mice with modified three-negative breast cancer cells that directly shut down the BBOX1 gene, preventing the growth of primary tumors.
in the second method, the researchers injected tumor cells into mice without affecting the growth of cancer cells until they became larger tumors.
then feed the mice with strong mycin, an antibiotic, to turn off the BBOX1 gene.
researchers found that the tumors stopped growing and shrinking.

. BBOX1's removal inhibits the occurrence of tumors of triple-negative breast cancer (Photo: Cancer Discovery) The team then added BBOX1-inhibited drugs to mice to replicate the results.
results show that these drugs are effective against tumors, have no negative effects on normal breast tissue or experimental animals as a whole, and have no detectable toxicity. Two of the BBOX1 inhibitors used in the
trials (C-2124 and AR692B) are still under study, and mildronate, another drug, has been approved in several European countries to increase oxygen in tissues to treat coronary artery disease. Dr.
, Dr. Zhang Qing believes that BBOX1 inhibitors, including Mildronate, could eventually become the target therapy that patients with triple-negative breast cancer have been waiting for.
": "At present, the treatment options of patients with triple-negative breast cancer are limited, resulting in poor clinical outcomes.
we think BBOX1 inhibitors may be a powerful weapon for the treatment of triple-negative breast cancer.
," Dr. Zhang added.
References: 1? Chengheng Liao, Yang Zhang, Cheng Fan, et al. Of The BBOX1 as a Met Target in Triple-Negative Breast Cancer (Source: Cancer Discovery) 2?Triple Breast Negative Cancer Vs. Match (University of Texas Southwest Medical Center)