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Immunotherapy-chemo combo extends life for women with aggressive form of breast cancer

By Chukwuma Muanya
25 October 2018   |   4:27 am
It is good news for women with triple-negative breast cancer, an aggressive and hard-to-treat form of breast cancer that targets women under 50.

CANCER IMMUNOTHERAPY… The next generation of cancer treatments

*Chinese tree compound helps destroy pancreatic tumours
*Fish oil diets could slow spread of malignant mammary cells
*Drug slashes ovarian tumour relapse in 63.3% of patients
*Blasting prostate growth with radiotherapy increases survival
*Switching to healthy diet extends colorectal sufferers’ lives

It is good news for women with triple-negative breast cancer, an aggressive and hard-to-treat form of breast cancer that targets women under 50.

A new study published Saturday in the New England Journal of Medicine found a combination of chemotherapy and antibody medications taught the women’s own immune system to attack cancer cells, in some cases extending life by almost a year.

“This is the first time immunotherapy has worked in such a difficult to treat cancer, and is a huge step forward for these breast cancer patients,” said lead author Dr. Peter Schmid of Queen Mary University of London, in a statement. He presented his findings at the European Society for Medical Oncology conference in Munich, Germany on Saturday.

“This is a real advance that is going to allow us to help more people,” said Memorial Sloan Kettering oncologist Dr. Larry Norton, who was not involved in the study. “Once we get regulatory approval, I think the expectation is this will change the standard of care.”

About one in ten of all breast cancers are triple-negative, according to the National Breast Cancer Foundation. It is most likely to affect Hispanic and African American women and those with a BRCA1 gene mutation. It also tends to attack women in their 40s and 50s.

“It is particularly tragic that those affected are often young,” Schmid said, and likely to still be raising families. “We have desperately been looking for better treatment options.”

When breast cancer cells test negative for estrogen, progesterone, or human epidermal growth factor 2 (HER2), it’s called a triple-negative breast cancer.

Therefore, it does not respond to any of the available hormonal cancer treatments.

It does respond to chemotherapy. However, for most women the cancer cells quickly develop resistance to the chemo. That allows the aggressive cancer to spread to other parts of the body, thus reducing survival rates.

In this trial, the combination of medication and chemo extended progression-free survival by at least 10 months, the study found. The chance of the cancer spreading to other areas of the body and the risk of death was also reduced by up to 40 per cent.

“This is just the beginning of using immunotherapy for breast cancer,” said Norton who serves as the director of the Evelyn H. Lauder Breast Center at the Memorial Sloan Kettering Cancer Center.

Scientists are learning “so much and so rapidly about other ways to stimulate the immune system,” Norton said, that he predicts an “explosion of well-designed studies that will push the agenda forward.”

How does it work? The new treatment combines the immunotherapy drug atezolizumab and traditional chemotherapy.

In a normal state, the immune system will not attack cancer cells because they are viewed as a part of the body. That’s where atezolizumab comes in. It’s an antibody that attaches to the cancer cell. It is job is to inactivate a protein called PD-L1, which is responsible for telling the immune system “don’t attack me.”

Chemotherapy is also needed, to “rough up” the exterior of the cancer cell, Schmid explained. That allows the newly revved-up immune system to recognize and attack the invader.

“We are using chemotherapy to tear away the tumor’s ‘immune-protective cloak,’ to expose it,” Schmid said, “enabling people’s own immune system to get at it.”

The Phase three study followed more than 900 women enrolled at 246 sites in 41 countries, who were randomly assigned to receive atezolizumab and chemo, or a placebo and chemo.

Standard chemotherapy was given every week. Atezolizumab was given intravenously every two weeks.

Also new study, published in the Journal of Experimental & Clinical Cancer Research, finds that a synthetic analog of a compound found in a rare Chinese tree can be used to tackle treatment-resistant pancreatic cancer.

New findings may drastically improve the outlook for people who have pancreatic cancer.

The American Cancer Society (ACS) reports that around 55,440 people will develop pancreatic cancer in 2018 and around 44,330 people will die as a result.

This cancer is particularly difficult to both treat and diagnose.

A lack of specific and accessible screening methods means that specialists often find the disease in its later stages, which can impact the patients’ outlook.

The ACS estimates that 12–14 percent of people with early-stage pancreatic cancer go on to survive for five years.

New research offers much-needed hope; scientists have found that a derivative of camptothecin — which is a Chinese tree bark compound whose anticancer properties were discovered over half a century ago — can effectively kill pancreatic cancer. tumours.

Fengzhi Li, Ph.D., who is an associate professor of oncology in the Department of Pharmacology and Therapeutics at the Roswell Park Comprehensive Cancer Center in Buffalo, NY, is the senior author of the new research.

As Li and colleagues explain in their new paper, one of the main challenges of treating pancreatic cancer is the fact that the tumors are particularly dense, making it difficult for drugs to penetrate.

In the past, researchers have tried to use thousands of synthetic analogs of camptothecin in the fight against pancreatic tumors, but the Food and Drug Administration (FDA) have only officially approved two.

However, both of these derivatives target a protein that not only fuels the growth of tumors but also is also key for the normal growth and renewal of tissue. Therefore, irinotecan and topotecan — the two FDA-approved camptothecin analogs — are highly toxic.

This is where Li and colleagues come in. In previous research, they developed another derivative of camptothecin that they called FL118, which they found to be effective against human colorectal cancer, as well as against head and neck cancer.

Importantly, FL118 does not work by inhibiting the aforementioned key protein, which makes it a lot less toxic.

In this study, Li and team tested FL118 and found that the compound destroyed drug-resistant cancer cells and prevented tumors from spreading by destroying cancer stem cells.

They carried out both in vitro and in vivo experiments, wherein they used cancer cell cultures as well as human-derived pancreatic cancer tumors, which they applied to animal models.

The experiments revealed that, when used alone, FL118 effectively destroyed pancreatic tumors. When used together with the common chemotherapy drug gemcitabine, FL118 helped destroy tumors that had previously resisted treatment with either gemcitabine alone or FL118 alone.

Overall, the drug was well tolerated and triggered none of the toxicity signs that irinotecan and topotecan produce.

“FL118’s high anticancer efficacy, along with its favorable toxicology profile, is consistent with the fact that this drug targets several key proteins involved in pancreatic cancer progression and treatment resistance,” says Li.

“Drugs that can more effectively reach and eliminate pancreatic tumors are urgently needed to treat this devastating disease,” he adds.

As Xinjiang Wang, co-corresponding study author, explains, “We believe that FL118 is promising new drug that can be further developed for the treatment of not only pancreatic cancer but also other types, such as colorectal cancer.”

“Our study provides strong support for the development of FL118-based therapies for pancreatic cancer, especially in patients who are resistant to current treatment.”

Meanwhile, Omega-3 fatty acids, such as those typically contained in fish oil, may suppress the growth and spread of breast cancer cells in mice. This is according to a new study in the journal Clinical & Experimental Metastasis, which is published under the Springer imprint. According to lead author, Saraswoti Khadge of the University of Nebraska Medical Centre in the US, fatty acids stopped further delayed tumors from forming, and blocked the cancerous cells from spreading to other organs in mice. The researchers speculate that this might be because of the way in which omega-3 fatty acids support the body’s immune and anti-inflammatory systems.

Two groups of adult female mice were fed a liquid diet for which the calorie count and percentage of fat that each contained were the same. The notable difference was that one diet contained plant oils rich in omega-6 polyunsaturated fats, and the other diet contained fish oil rich in omega-3 fatty acids. The mice were then injected with 4T1 breast cancer cells that cause aggressive tumors to develop in the breast. These cells are known to spread spontaneously to other parts of the body, such as bones, the lungs and liver, but less frequently to the heart, kidneys and ovaries. The mice were autopsied and studied 35 days after the breast cancer cells were injected.

Khadge and her colleagues found the chance that the breast cancer cells would take hold in the breast glands of the adult female mice was significantly lower in those on the omega 3-diet. Tumors took significantly longer to start developing in these mice, and this had an influence on their size. After 35 days, the tumors detected in their breasts were 50 per cent smaller than those that developed in the omega 6-group. The likelihood of the cancerous cells growing and spreading to other organs in the omega-3 group was also lower and these mice survived longer than those on the omega-6 diet. Indeed some of the omega-3 fed mice appeared to never develop breast cancer.

More T-cells were found in the tissue of the mice in the omega-3 group than in the omega-6 group, and these correlated with dying tumor cells. This is important because T-cells are white blood cells that play a role in strengthening the immune system against tumors. The mice fed an omega-3 diet also had less inflammation. According to Khadge this could mean that a diet rich in omega-3 fatty acids helps to suppress the type of inflammation that can trigger the rapid development and spread of tumors as well as promote T-cell responses to tumours.

“Our study emphasizes the potential therapeutic role of dietary long-chain omega-3 fatty acids in the control of tumor growth and metastasis,” explains Khadge, who emphasizes that this does not mean that an omega-3 diet could summarily prevent breast cancer tumors from forming altogether.

This study is based on dietary consumption during adult life. Its findings are in line with previous studies that showed how eating fish oil based diets during pregnancy and as a child markedly suppresses the development and spread of breast cancer.

Meanwhile, a breakthrough treatment for ovarian cancer slashes the chance of it returning, a study has found.

Two thirds of patients given the drug during a trial had not relapsed within three years, compared to a third among those who were given a placebo, which doctors described as ‘exciting’.

Ovarian cancer is notoriously difficult to treat, as the majority of cases are not diagnosed until it has spread. Just over a third of women are still alive a decade after diagnosis.

Olaparib, the first in a revolutionary class of treatments developed in British universities, has already been found to extend the lives of severely ill women with the disease.

In the latest study, 260 women with the BRCA gene mutation were given the pill while 130 others were given a placebo. All also underwent surgery and chemotherapy, as is standard.

Half of those given the treatment are still showing no signs of the disease returning since the trial began in 2013, according to the findings published in the New England Journal of Medicine.

Professor Charlie Gourley, from the University of Edinburgh which led the British part of the international trial, said: “The most exciting finding is that more than half the patients on the olaparib arm have not relapsed. This is unprecedented and raises the possibility that a number of these patients may be cured.”

Olaparib, sold under the brand name Lynparza, is the first of a group of drugs called PARP inhibitors that exploit a weakness in cancer cells’ defences.

Because it is already used to treat women whose ovarian cancer has returned, it could quickly be approved for use.

Meanwhile, targeting the source of advanced prostate cancer with radiotherapy after the disease has spread can increase survival chances by 11 per cent.

Experts say the ‘monumental findings’ could change how advanced cancers are treated.

Patients whose prostate cancer has spread are typically given hormone therapy to reduce or stop the production of testosterone, as the molecule can encourage the cancer’s growth.

But these findings suggest radio- therapy – which uses high-energy radiation to kill cancer cells – is also effective.

It was previously thought there would be little benefit in blasting the prostate tumour if the disease had spread to other parts of the body.

Professor Charles Swanton, Cancer Research UK’s chief clinician, said: “This is a monumental finding that could help thousands of men worldwide. Adding radiotherapy to current treatment shows clear benefit for this subgroup of men with prostate cancer.

“If we can understand exactly why these men benefit from the additional radiotherapy treatment, we could hopefully use this approach to benefit even more patients.”

In the study, scientists enrolled 2,000 men who were all at an advanced stage of the disease in the clinical trial. Half were given standard treatment while the other half received standard treatment and radiotherapy to the prostate – the site of the primary tumour.

Among men treated with additional radiotherapy whose cancer had spread to their lymph nodes and or bones nearby, researchers found that around 80 per cent survived for at least three years. This fell to 70 per cent of men who were given the standard hormone treatment. No benefit was seen among men whose cancer had spread further, according to the findings published in The Lancet.

Also, switching to a healthy diet could help extend survival times for colorectal cancer sufferers, new research has found.

Though the cancer’s causes are complex, obesity is known to be a significant risk factor, so eating a healthy, balanced diet low in sugary, salty and processed foods can keep risks to a minimum.

But new American Cancer Society research shows that even diet changes made after a cancer diagnoses can help patients live longer lives.

Colorectal cancer has become the fourth most common cancer in the US, and rates have surged in recent years.

It is striking, and killing, more young people than ever. Every year, 1.4 percent more people under 55 die of colorectal cancer.

And now, new research suggests that eating well is not just preventative, but helps to extend the lives of cancer sufferers.

When it’s caught early, colorectal cancer is often curable, with about a 90 percent survival rate.

But making lifestyle changes may be key those survival rates. To that end, Dr. Mark Guinter and his team analyzed data on 2,801 people that had been diagnosed with colorectal cancer and their eating habits.

Some of the patients, according to the American Cancer Society (ACS), adhered to its health and nutrition guidelines.

The ACS advises people to avoid any excess fat, avoid high calorie foods and drinks and instead eat fruits, vegetables, and to limit the amount of red or processed meat they eat.

Alongside these dietary suggestions, the ACS suggests getting at least 150 minutes of vigorous exercise a week and keeping a healthy, regular sleep schedule.

The advocacy group encourages people to keep up all of these good habits starting as early as possible and throughout life.

But the new study found that those who kept to the ACS’s guidelines – even if they didn’t pick up the better habits until after their diagnoses – had a 20 percent lower risk of death.

By contrast, those who ate a ‘Western diet,’ which consists of a large proportion of red meat, processed foods and other animal products, had the highest risk of death of any category of colorectal cancer patients.

“This study is this first to our knowledge that considered change in diet quality across the colorectal cancer continuum,” said Dr. Guinter.

“These results suggest that high diet quality after diagnosis, even if poor before, may be associated with a lower risk of death.”

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