Cancer Dis: A new breakthrough in targeted treatment for three negative breast cancers! The BBOX1 gene is the key!

!----: Triple-negative breast cancer (TNBC) accounts for about 15-20% of all breast cancers and is known for its poor differentiation, high aggressiveness, and easy metastasis.in the era of precision treatment, three-negative breast cancer because there is no specific target, often to chemotherapy-based, clinical treatment is more difficult.effective treatment target has always been a worldwide problem in the academic community.researchers at the University of Texas Southwestern Medical Center (UTSW) in a new study, said one of the oxygen-sensitive enzyme family can provide a viable target for triple-negative breast cancer (TNBC).'s findings, published online this week in the journal Cancer Discovery, may offer hope to this segment of the patient.triple-negative breast cancer patients have few effective treatment options and often have a poor prognosis.TNBC is called TNBC because it lacks estrogen receptors, progesterone receptors, and over-expression of the growth-promoting HER2 protein, accounting for 15 to 20 percent of all breast cancers.However, Dr. Qing Zhang, an associate professor in the Department of Pathology at the University of Texas and a cancer research scholar at the Texas Cancer Prevention Institute (CPRIT), explained that TNBC is the deadliest of all breast cancers, with a five-year survival rate of 77 percent and a five-year survival rate of 93 percent for other types of breast cancer.unlike other hormone-receptor-positive or HER2-positive cancers, TNBC has no targeted treatment, and patients rely on surgery, chemotherapy, and radiotherapy, which are less effective than targeted treatments and can damage healthy tissue.'s lab to study how cancer survives in low-oxygen environments.to find a viable drug target for TNBC, Zhang and his colleagues focused on the 2-ketone diacid (2OG)-dependent enzyme, a family of 70 enzymes, some of which act as oxygen sensors in cells.to determine their role in TNBC, the researchers used a library of short-disturbing RNA (a fragment of genetic material that closes the expression of specific genes) to shut down family members who depend on 2OG in different TNBC and healthy breast cell lines.they quickly focused on a specific 2-hydroxyl dependent molecule, the gamma-dibutadal hydroxylase 1 (BBOX1), known as the promotion of cell-synthetic carnitine, a molecule that plays a key role in energy metabolism.when the researchers shut down the gene responsible for producing BBOX1, the TNBC cells stopped dividing and eventually died, but turning it off in a healthy breast cell line had no effect.and vice versa: overexpression of the BBOX1 gene leads to the widespread proliferation of TNBC cell lines. further researchshowed that it was not carnitine, the end product of the enzyme, that caused the result.enzyme itself seems to be the key to the survival and growth of TNBC cells. to study how BBOX1 works, Zhang and his colleagues looked at which proteins the enzyme interacts with in cells. their experiments, BBOX1 is uniquely linked to a protein called IP3R3, which previous studies have linked to other malignant tumors. IP3R3 is important to help mitochondria (the organ, which acts as a source of cell energy), extract energy from sugar. by binding to this protein, BBOX1 prevents it from degrading, giving TNBC cells the energy they need to grow. on the other hand, eliminating BBOX1 has the potential to stop the development of TNBC tumors. researchers demonstrated this in mice, injecting them with modified TNBC cells so that the BBOX1 gene could be turned off directly or by feeding the mice an antibiotic called strong mycomycin. turning off the BBOX1 gene in these cancer cells will stop the growth of primary tumors. in another strategy to simulate breast cancer growth and treatment, researchers injected tumor cells into mice, allowing TNBC cells to grow uninhibited into larger tumors. then injected the mice with strong penicillin to turn off the BBOX1 gene. they found that these tumors stopped growing and contracting. Zhang's team also got the same result by giving mice drugs that inhibited BBOX1. these drugs are effective against TNBC tumors, but have no negative effects on normal breast tissue or the animal as a whole, nor are they detectable toxicity. notes that while two of the drugs are still being developed, one of them, mildronate, has been used in some European countries to increase tissue oxygen supply to treat coronary artery disease. this or other BBOX1 inhibitors could end up being a long-awaited target treatment for TNBC patients. .