Research Progresses on Breast Cancer

Breast cancer is the most common cancer among women worldwide, which is a disease in which breast cells grow out of control. Breast cancer is the second leading cause of cancer deaths in American women (after skin cancer), causing more than 42,000 deaths each year. The breast is composed of three main parts: lobules, ducts and connective tissue. The lobules are glands that produce milk. The catheter is the tube that carries milk to the nipple. Connective tissue (composed of fibrous tissue and fatty tissue) surrounds and holds the above things together. Most breast cancers start in ducts or lobules. Symptoms of breast cancer include breast lumps, bleeding from the nipple, or changes in the shape or texture of the nipple. Breast cancer can spread outside the breast through blood vessels and lymphatic vessels. Scientists are actively working to develop more drugs and treatments that benefit breast cancer patients. The following are some of the latest progresses in breast cancer research.

1 A new combination therapy that effectively treats breast cancer was successfully developed

Scientists from Monash University and other institutions have developed a new type of combination therapy, which may be expected to help treat breast cancer patients with specific gene mutations. PTEN is a special gene that can inhibit tumor progression. Researchers conducted studies on animal models and organoids and performed proteomic screening, and found that the loss of PTEN and PI3K gene mutation can synergize to form tumors in breast tissue. Later they found that inhibiting the function of AKT protein could effectively block the growth of breast organoids with mutations in PTEN and PI3K. Researchers also found that loss of PTEN function increases the level of glucocorticoid receptor (GR) and makes tumor cells more prone to death. Dexamethasone is a widely used drug at present, which can effectively activate the expression of GR. Combining dexamethasone with an AKT inhibitor may inhibit the growth of PTEN/PI3K mutant cancer cells better than a single compound. Scientists are currently testing the efficiency of this combination therapy in preclinical animal models. Recently, this research was published in Molecular Cell.

2 Olaparib for the treatment of breast and ovarian cancer will lead to a revolution in the treatment of advanced prostate cancer

The final results of a phase III clinical trial showed that olaparib, a pioneering drug called PARP inhibitor, also the first anti-cancer drug that targets genetic defects can be successfully used to treat prostate cancer that has a weak ability to repair damaged DNA. This innovative drug is more effective than the modern hormone drugs abiraterone and enzalutamide in slowing the growth and spread of advanced prostate cancer. The previous results of this clinical trial led to olaparib being approved by the U.S. Food and Drug Administration (FDA) as one of the first gene-targeted drugs that can be used to treat prostate cancer. Related research results were recently published in NEJM, with the title “Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer”.

3 New research reveals risks of breast cancer drugs

Recently, a new study led by Flinders University has found a link between beta-blockers, which are commonly used to treat cardiovascular diseases, and the survival outcomes of certain breast cancer patients. According to a new paper in Frontiers In Oncology, β-blockers are negatively correlated with the survival outcomes of patients with HER2-positive advanced breast cancer. The study showed that patients in the HER2-positive ABC group who used β-blockers had worse survival outcomes compared with patients who did not use β-blockers. This study concluded that “future research should aim to gain a deeper understanding of the effects of beta blockers on specific breast cancer subtypes, cancer types and cancer treatments.”

4 The “hierarchy” of breast cancer cells may be a potential cause of inducing patient tolerance to therapy

Scientists from the University of Cincinnati found that breast cancer seems to take different forms or life stages to promote the growth and spread of cancer cells. The relevant research results were published in eLife. When it comes to breast cancer, we all know that the diversity of cells in breast tumors poses a problem for the treatment of patients, because specific subgroups of tumor cells may become resistant to the therapy and eventually lead to the recurrence of breast cancer. One factor leading to this diversity of cells is that tumor cells can survive in different cell states, can be transformed into stem cell-like cells of other cell types, and can also be used as more differentiated cells responsible for specific purposes or specific functions. Cancer cells with stem cell-like properties are often considered to induce drug resistance, and they are also at the top of the tumor hierarchy, such as the role of “king” or “queen”, while the most differentiated tumor cells are at the bottom, just like ordinary residents. In this study, researchers used breast cancer animal models to determine the hierarchy of tumors other than “ruler cells” and “ordinary cells”. They identified and classified individual cells, which may help them understand the function of each single cell.

5 Nanotechnology combined with immunotherapy can help treat breast cancer

Recently, a study led by researchers from Case Western Reserve University School of Medicine has made great progress in combating deadly metastatic breast cancer by combining nanotechnology with immunotherapy. When a tumor appears in the human body, our immune cells should recognize the tumor and send out cells to try to “kill and remember the enemy” so that they can come back and kill the tumor cells again if the tumor recurs. But when the tumor adapts to the immune environment in the body, it will be in a state of being covered up, so it cannot be detected by the immune system. Efstathios Stathis Karathanasis, associate professor of biomedical engineering, directed the development of this new technology. His team designed a nanoparticle that can be sent into the body to wake up “cold” tumors, allowing them to be localized and neutralized by immune cells.

6 Special protein BIK may promote breast cancer to worsen

Scientists from the University of Alberta and other institutions have discovered a special protein BIK that is directly related to the poor prognosis of breast cancer patients. Relevant research results are published in Cell Death and Disease, which may help scientists develop new breast cancer treatments in the future. In ER-positive breast cancer (breast cancer in which cancer cells can respond to estrogen), when BIK is induced to express, cell apoptosis cannot be completely completed, but will undergo the so-called “apoptosis failure”, that is, the DNA in the cell is destroyed to form mutations, which will make cancer cells more aggressive. The researchers plan to continue to study BIK in depth and find more information to clarify how it plays a role in the process of apoptosis.

7 Bee toxin can be used to kill malignant breast cancer cells

Researchers from the Harry Perkins Institute of Medical Research and the University of Western Australia used the venom of 312 bees and bumblebees from Perth, Western Australia, Ireland and England to test the effect of the venom on clinical subtypes of breast cancer. The results show that bee venom can effectively kill triple-negative breast cancer cells and breast cancer cells that highly express HER2. Dr. Ciara Duffy said, “The purpose of this study is to study the anti-cancer properties of bee venom and a melittin component on different types of breast cancer cells. We found that a certain concentration of bee venom can induce 100% of cancer cells to die, and its effect on normal cells is very small. In addition, we found that melittin can completely destroy cancer cell membranes within 60 minutes. Melittin regulates signal transduction in breast cancer cells by inhibiting the activation of receptors (epidermal growth factor receptor) that are usually overexpressed in triple negative breast cancer, and inhibits the activation of HER2 overexpressed in HER2-rich breast cancer. This study provides an excellent example of how natural compounds can be used to treat human diseases.” This research was recently published in Precision Oncology.

8 New combination therapy can block the transfer of breast cancer cells to the brain

Breast cancer can spread to other organs, such as the brain, lungs, and bones. The metastasis of breast cancer to the brain is generally considered a terminal illness. Clinical statistics show that women with HER2-positive breast cancer are prone to brain metastases in up to 55% of cases. For breast cancer cells that have metastasized to the brain, current chemotherapy drugs are usually ineffective because they cannot cross the blood-brain barrier. A new research report shows that a new combination therapy for breast cancer tumors in the brains of mice can significantly reduce tumor size and increase survival rates. Approximately 75% of mice with breast cancer brain metastases can achieve complete cure after treatment. The two drugs are the tubulin inhibitor vinorelbine and the bromine inhibitor I-BET-762. Vinorelbine has been approved by the FDA for clinical use, and the bromine inhibitor I-BET-762 has been approved for clinical trials. Dr. Maciej Lesniak, professor of neurosurgery at Northwestern University’s Feinberg School of Medicine and professor of Northwestern Medical Neurosurgery, said: “The new combination therapy we have developed can cross the blood-brain barrier and significantly improve survival.” The research paper was recently published in Science Translational Medicine.

9 High levels of interleukin 34 (IL-34) are associated with triple negative breast cancer

According to the combination of cell receptor molecules present on the surface of cancer cells, breast cancer can be divided into three types: Luminal A, Luminal B and HER2+. In addition, there is a fourth type of breast cancer, triple negative breast cancer (TNBC). This type of breast cancer does not have any of the above three receptors, so it does not respond to standard treatments and its prognosis is usually worse than other types of breast cancer. As we all know, interleukin 34 (IL-34) is closely related to the poor prognosis of lung and liver cancer. A group of scientists from the Institute of Genetic Medicine (IGM) of Hokkaido University recently discovered that there is a link between IL-34 and triple-negative breast cancer, and IL-34 can be used to assess the prognosis of TNBC patients. The researchers analyzed data from 1083 breast cancer patients and found that TNBC was associated with high levels of IL-34. Professor Ken-ichiro Seino, head of the Department of Immunology of IGM, said: “Currently chemotherapy is the only reliable method for the treatment of TNBC, but patients often develop resistance to chemotherapy. Our findings indicate that IL-34 is a potential molecule for the treatment of TNBC.”

10 Precision medicine helps treat triple-negative breast cancer

Triple-negative breast cancer is a highly aggressive subtype of breast cancer, accounting for 15-20% of breast cancer cases, but 25% of total breast cancer deaths. Senior scientist Dr. Mathieu Lupien said: “There is no precise medicine for this disease, so patients have to receive chemotherapy. At first, chemotherapy is effective for some patients, but within five years after diagnosis, nearly a quarter of patients have cancer recurrence. Many patients will even develop chemotherapy-resistant tumors.” Recently, researchers from Princess Margaret studied the changes in the metabolism of cancer cells and tried to use these molecular changes to help them develop precise drugs. In this study, researchers found a promising method that uses specific protein biomarkers to identify patients suitable for targeted therapy. Using patient cell lines derived from triple negative breast cancer, the researchers tested their sensitivity to the metabolic inhibitor GLUT1. They found that there is an association between RB1 (a protein involved in cell metabolism) and tumor suppressor proteins, and the growth of these cancer cells is inhibited. This study shows that different levels of RB1 expression can be used as biological biomarkers to distinguish patients’ sensitivity to drugs in the future. This research was recently published in Nature Communications.