Osteoporosis drug prevents spread of basal-like breast cancer in mice

In continuation of my update on zoledronic acid 

Researchers in China have discovered that an enzyme called UGT8 drives the progression of basal-like breast cancer, an aggressive form of the disease that is largely untreatable. But the study, which will be published May 4 in the Journal of Experimental Medicine, reveals that the widely used osteoporosis drug zoledronic acid inhibits UGT8 and prevents the spread of basal-like breast cancer in mice, suggesting that this drug could also be used to treat the disease in humans.

Basal-like breast cancer is a particularly aggressive form of breast cancer that typically affects younger, premenopausal women. It is hard to treat because the tumor cells are usually "triple negative," lacking the estrogen receptor, progesterone receptor, and HER2 protein that are the main therapeutic targets for other forms of breast cancer. As a result, the prognosis for patients with basal-like breast cancer is worse than any other breast cancer subtype.

"The highly aggressive nature and the absence of effective therapeutics for basal-like breast cancer make it a high priority to elucidate what determines its aggressiveness and identify potential therapeutic targets," says Professor Chenfang Dong from the Zhejiang University School of Medicine in Hangzhou, China.

Cancer cells must alter their metabolism in order to survive and metastasize to other parts of the body. Dong and colleagues examined over 5,000 breast cancer patient samples and found that levels of the metabolic enzyme UGT8 were dramatically elevated in patients with basal-like breast cancer. Higher UGT8 levels correlated with increased tumor size, higher tumor grade, and shorter patient survival times.

UGT8 catalyzes the first step in the synthesis of sulfatide, a type of lipid that is found on the surface of cells and has been implicated in cancer progression. Dong and colleagues found that breast cancer cells expressing high levels of UGT8 produce large amounts of sulfatide, which in turn activates signaling pathways crucial for the survival and metastasis of basal-like breast cancer. Depleting UGT8 from these cells lowered sulfatide levels and reduced the cells' ability to form tumors when injected into mice.

Zoledronic acid is a drug that is approved to treat a variety of bone diseases, including osteoporosis, and is on the World Health Organization's list of safe and effective medicines essential for global health. Dong and colleagues confirmed that zoledronic acid is a direct inhibitor of UGT8 that reduces the levels of sulfatide in basal-like breast cancer cells. Treatment with the drug impaired the cells' ability to invade their surroundings and, accordingly, prevented them from metastasizing to the lungs after they were injected into the mice.

"Our study suggests that UGT8 contributes to the aggressiveness of basal-like breast cancer and that pharmacological inhibition of UGT8 by zoledronic acid offers a promising opportunity for the clinical treatment of this challenging disease," Dong says.​

Ref :http://jem.rupress.org/content/early/2018/05/03/jem.20172048

Zoledronate drug can protect stem cells from ageing

In continuation of my update on Zoledronic acid..

Stem cells can be protected from the effects of ageing by a drug currently used to treat patients with osteoporosis, a breakthrough study has found.

Scientists from the University of Sheffield discovered the drug zoledronate is able to extend the lifespan of mesenchymal stem cells by reducing DNA damage.

DNA damage is one of the most important mechanisms of ageing where stem cells lose their ability to maintain and repair the tissues in which they live and keep it working correctly.

The pioneering research shows the drug protects the stem cells from DNA damage enhancing their survival and maintaining their function.

Professor Ilaria Bellantuono, from the University's Department of Metabolism, said: "The drug enhances the repair of the damage in DNA occurring with age in stem cells in the bone. It is also likely to work in other stem cells too.

Zoledronate drug can protect stem cells from ageing

Atorvastatin drug plus zoledronic acid may help treat toxoplasmosis

In continuation of my update on Atorvastatin and Zoledronic acid

Researchers at the University of Georgia have discovered that a combination of two commonly prescribed drugs used to treat high cholesterol and osteoporosis may serve as the foundation of a new treatment for toxoplasmosis, a parasitic infection caused by the protozoan Toxoplasma gondii. They published their findings recently in PLOS Pathogens.

Toxoplasma gondii is a parasite capable of infecting nearly all warm-blooded animals. While healthy human adults usually suffer no lasting ill effects from infection, it can be harmful or fatal to unborn fetuses or those with weakened immune systems.

"For many years, therapies for toxoplasmosis have focused on drugs that target only the parasite," said Silvia Moreno, senior author of the article and professor of cellular biology in UGA's Franklin College of Arts and Sciences. "But in this paper, we show how we can hit the parasite with two drugs simultaneously, one that affects body chemistry in the host and one that affects the parasite."

The UGA researchers discovered that a combination of the cholesterol lowering drugatorvastatin and osteoporosis medication zoledronic acid, both more commonly known by their respective trade names, Lipitor and Zometa, produce changes in the mammalian host and in the parasite that ultimately block parasite replication and spread of the infection.

"These two drugs have a strong synergy," said Moreno, who is also a member of UG

A's Center for Tropical and Emerging Global Diseases. "The mice we treated were cured from a lethal infection using this combination approach."

Moreno and her colleagues began working on this drug combination following a series of experiments with unexpected results. They created a genetically modified version of the parasite in the laboratory that lacked a specific enzyme essential for one of the organism's most basic functions.

Atorvastatin drug plus zoledronic acid may help treat toxoplasmosis

Zoledronic Acid Shows Long-Term Benefit in Survivorship for Premenopausal ER-Positive Breast Cancer

In continuation of my update on Zoledronic acid....

Zoledronic Acid Shows Long-Term Benefit in Survivorship for Premenopausal ER-Positive Breast Cancer

Osteoporosis drug reduces bone loss in oral cancer

In continuation of my update on zoledronic acid....
Osteoporosis drug reduces bone loss in oral cancer

Bone drug (Zoledronic acid) suppresses wandering tumor cells in breast cancer patients

In continuation of my update on zoledronic acid, I find this info really  interesting.  Researchers from Washington University School of Medicine in St. Louis, have found that the bone-strengthening drug zoledronic acid (Zometa) can help fight metastatic breast cancer when given before surgery.

When the drug was given along with chemotherapy for three months before breast cancer surgery, it reduced the number of women who had tumor cells in their bone marrow at the time of surgery.

Tumors shed thousands of cells, which spread throughout the body and are referred to as disseminated tumor cells (DTCs). Breast cancer DTCs often lodge in bone marrow where bone growth factors help them survive.

Chemotherapy can increase bone turnover and bone growth factors, potentially exacerbating the problem of DTCs in the bone, which can resurface later to cause metastatic disease in cancer patients.

Researchers believe that zoledronic acid inhibits the release of growth factors that help support the growth of DTCs.

In this randomized phase II clinical trial, researchers split 109 women with newly diagnosed stage II or stage III breast cancer into two groups. The control group received chemotherapy alone, while the other received a combination treatment of chemotherapy and zoledronic acid. After three months of therapy, patients with DTCs in their bone marrow decreased from 43 percent to 30 percent in the combination group, compared with a decrease from 48 percent to 47 percent in the control group. This result approached statistical significance.

Zoledronic acid treatment with chemotherapy had additional benefits. Women in the combination group experienced significant gains in bone density after 12 months. This is helpful for breast cancer patients, who often develop osteoporosis as a side effect of chemotherapy and other breast cancer treatments.  

The study also suggested that zoledronic acid may help fight certain types of breast tumors directly. Aft speculates that the drug may stop the tumor from making its own blood supply, modify the immune system in a way that makes it harder for tumor cells to survive or even cause the cancer cells to commit suicide.....

Ref : http://www.ncbi.nlm.nih.gov/pubmed/20362507?dopt=Abstract

Bisphosphonates play a role in reducing recurrent breast cancer....

We know that bisphosphonates (also called diphosphonates) are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases. Bone has constant turnover, and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts digesting bone. Bisphosphonates inhibit the digestion of bone by osteoclasts. Osteoclasts also have constant turnover and normally destroy themselves by a process called cell suicide (apoptosis). Bisphosphonates encourage osteoclasts to undergo apoptosis. Though other uses like in he treatments of osteoporosis, osteitis deformans, bone metastasis, primary multiple myeloma,hyperparathyroidism and osteogenesis imperfecta were known. A new data suggests that these agents may play a role in reducing recurrent breast cancer as well. Zoledronic acid (see the structure) is both safe and effective in preventing bone loss in postmenopausal women with breast cancer who are treated with aromatase inhibitors, according to data presented at the CTRC-AACR San Antonio Breast Cancer Symposium. Women who take aromatase inhibitors need some sort of bone protection, and this five-year data show that zoledronic acid is a viable option.

As per the claim by the researchers lead by Dr. Adam Brufsky , women who are on Medicare tend to go with tamoxifen because the cost of anastrozole puts them squarely in the donut hole of Medicare Part D, but once the cost barrier is removed there will likely be a mass switch to the aromatase inhibitor, which will necessitate the need for bone protection. More interestingly, in the same conference a research group lead by Rowan Chlebowski presented a study wherein "women who used bisphosphonates, had significantly fewer invasive breast cancers than women who did not use bisphosphonates. .......

http://www.upci.upmc.edu/news/upci_news/121009_study.cfm