Study discovers targeted therapy to help adolescents with deadly nerve cancer

A targeted therapy has been discovered to treat adolescent patients who suffer from a deadly paediatric nerve cancer called neuroblastoma, a recent study has stated.


Neuroblastoma is one of the most common and aggressive paediatric nervous system tumours and generally has a poor prognosis, particularly when it advances in older children.

Treatment success for the disease varies, but is exponentially less in adolescent patients, particularly because the disease lacks effective targeted therapies.

The Mount Sinai researchers found that neuroblastoma in older children and adolescents harbouring deletions within a gene called ATRX may be responsive to a targeted therapy called tazemetostat.

Tazemetostat disables an enzyme called EZH2 that inhibits genes that promote normal neuron development, in turn killing neuroblastoma cells. Neuroblastoma arises in immature nerve cells of the adrenal glands and portions of the spine during the development of the sympathetic nervous system, which controls the body's "flight or fight" response to stress.

EZH2 inhibitors are already being tested in phase I and phase II clinical trials for other cancers, including lymphomas, sarcomas, and other solid tumours, with some favourable results.

"We hypothesised that mutant ATRX proteins contribute to aggressive neuroblastoma," said a Professor of Oncological Sciences and senior corresponding author.

"In this study, we aimed to decipher the underlying biology of these altered proteins in neuroblastoma, a tumor for which effective therapeutic strategies remain obscure, and to exploit identified dependencies," added the Prof.

Mount Sinai scientists continue to expand this research into the role of the mutant ATRX protein in the laboratory and hope to eventually open a clinical trial with collaborating institutions.

Based on this research, they believe that EZH2 inhibitors could also be effective in other ATRX mutant cancers, such as pediatric glioblastoma, multiforme and osteosarcoma.

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Turmeric promotes growth of healthy bone cells

Researchers developed a new drug delivery system with the help of curcumin, the main ingredient in the spice turmeric, which successfully prevents bone cancer cells to spread and promote the growth of healthy bone cells.

The work could lead to better post-operative treatments for people with osteosarcoma, the second most prevalent cause of cancer death in children, reported by researchers.

Young patients with bone cancer are often treated with high doses of chemotherapy before and after surgery, many of which have harmful side effects. Researchers would like to develop gentler treatment options, especially after surgery when patients are trying to recover from bone damage at the same time that they are taking harsh drugs to suppress tumour growth.

Turmeric has been used in cooking and as medicine for centuries in Asian countries, and its active ingredient, curcumin has been shown to have anti-oxidant, anti-inflammatory and bone-building capabilities. It has also been shown to prevent various forms of cancers.

"I want people to know the beneficial effects of these natural compounds. Natural biomolecules derived from these plant-based products are inexpensive and a safer alternative to synthetic drugs," said the Dr. However, when taken orally as medicine, the compound can't be absorbed well in the body. It is metabolized and eliminated too quickly.

In their study, the researchers used 3D printing to build support scaffolds out of calcium phosphate. While most implants are currently made of metal, such as ceramic scaffolds, which are more like real bone, could someday be used as a graft material after bone cancer surgery. The researchers incorporated curcumin, encapsulated in a vesicle of fat molecules into the scaffolds, allowing for the gradual release of the chemical.

The researchers found that their system inhibited the growth of osteosarcoma cells by 96 per cent after 11 days as compared to untreated samples. The system also promoted healthy bone cell growth.
"This study introduces a new era of integration where modern 3d printing technology is coupled with the safe and effective use of alternative medicine, which may provide a better tool for bone tissue engineering," said the Dr.

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This natural sugar supplement could help fight cancer

Mannose-- a nutritional supplement -- found naturally in fruits such as cranberries can aid in slowing the growth of tumours and improve cancer treatment, a study has shown.

The findings showed that mannose enhanced the effects of chemotherapy in mice with multiple types of cancer including leukaemia, osteosarcoma, ovarian and bowel cancer. It slowed tumor growth, reduced the size of tumours and even helped increase the lifespan of some mice.

Tumours use more glucose than normal, healthy tissues. However, it is very hard to control the amount of glucose in your body through diet alone. Researchers found that mannose can interfere with glucose to reduce how much sugar cancer cells can use.

"Tumours need a lot of glucose to grow, so limiting the amount they can use should slow cancer progression. The problem is that normal tissues need glucose as well, so we can't completely remove it from the body. 

"In our study, we found a dosage of mannose that could block enough glucose to slow tumour growth in mice, but not so much that normal tissues were affected," said the lead author of the study.
 
"This is early research, but it is hoped that finding this perfect balance means that, in the future, mannose could be given to cancer patients to enhance chemotherapy without damaging their overall health," he added.

For the study, the team first examined how mice with pancreatic, lung or skin cancer responded when mannose was added to their drinking water and given as an oral treatment. They found that adding the supplement significantly slowed the growth of tumours and did not cause any obvious side effects.

To test how mannose could also affect cancer treatment, mice were treated with cisplatin and doxorubicin -- two of the most widely used chemotherapy drugs. 

Some cells responded well to the treatment while others did not. It was also found that the presence of an enzyme that breaks down mannose in cells was a good indicator of how effective treatment was.



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Why Surgeons Amputated Child's Leg, Reattached It The Wrong Way

Not long before her 7th birthday, a young girl, a small dancer with big dreams of performing on stage, received a devastating diagnosis.

Doctors discovered a 10-centimeter tumor in the femur in her left leg -- and it had broken the bone, according to doctors. When it did not respond to chemotherapy, doctors told her parents that the limb would need to be amputated, but they had a solution to help the active child maintain her mobility, according to the news.

During a rare and complex medical procedure this year, surgeons in central England amputated her leg at the thigh, removed the central portion and then reattached the lower leg to the upper leg - backward. The young girl will eventually be able to use her ankle as a knee joint and simply fit her foot into a prosthetic so she can walk, run and dance once again.

"It doesn't feel that different," she said, tracing the scars on her leg. "But it is different when I have to move 'cause it's the other way around -- when I move it up or down or side to side, I go the other way 'cause it's the wrong way around."
 
The girl was diagnosed last year with a form of bone cancer called osteosarcoma, or osteogenic sarcoma, according to doctors.

Her mother,  told that her daughter's leg "gave way" while she was playing last summer, and although her parents tried to nurse the injury, her limb continued to swell.

The mother took her daughter to a nearby hospital, and was then sent to a Children's Hospital, where doctors confirmed the diagnosis, she said.

"I called my husband, and when they took us into a room with comfy chairs and tissues, I knew it was bad news," the mother said.

Osteosarcoma, which is the most common type of bone cancer in children, typically affects the femur and tibia in the upper and lower leg and the humerus in the upper arm, according to the Hospital. When treated early, the long-term survival rate is 70 to 75 percent, according to the children's hospital.

Such tumors can be treated with chemotherapy or surgery, such as rotationplasty - a procedure most commonly used to treat tumors in children in which the lower leg is turned 180 degrees, essentially turning the ankle into a knee.

In January, the young girl had the operation.

A surgeon who performed the procedure, said this week that before she went into surgery, she bid farewell to the "loser" tumor.

"She was the perfect patient to have this procedure and even said 'goodbye loser' to the cancer as we prepared to amputate," he said in the statement.

"She has shown real bravery and confidence in showing off her leg, even though it looks a bit different. I'm glad that she'll be able to continue doing all the things a normal child can do including sports and dancing."

The girl's mother could not immediately be reached for comment but told that the procedure was her daughter's best option.

"This way, she'll be able to then get a prosthetic leg," the mother said, telling her 7-year-old daughter that she will be able to "do all the things you used to love to do and all your and all your sports and your dancing."

Family members and friends have started donating to a JustGiving page to help the child's parents keep her fitted with prosthetic activity blades.

In the end, the girl's mother said she thinks her daughter's dream will come true.

"The girl has always been an active child, she attended various clubs: Swimming, athletics at school, street dancing, ballet and tap, acrobatics and gymnastics. In addition she loves riding her bike and running. She dreams one day to return to dancing and perform on a stage," the mother told about her child. But the mother added that since the surgery this year, her daughter has also developed some new dreams. "She talks of how her new leg will enable her to travel the world one day and maybe even enter the Paralympics."
 
"People ask how we cope, but we take our lead from the girl, she has been so positive about all this," the mother told the news site. "She has been so brave through all this -- just before her surgery she waved to her leg and said 'bye, bye tumor, see you loser!' After her surgery, one of the nurses overheard her say to another child: 'There's nothing wrong with being different.' "

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