Cancer

Scientists are genetically engineering Salmonella to destroy brain tumours

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Salmonella is commonly linked to fevers and food poisoning, and generally speaking, it isn’t good news at all for your body. But scientists have come up with an exception: a genetically engineered form of Salmonella bacteria that can eat away at cancer tumours.

The modified bacteria target tumours in the brain rather than seeking out the human gut where Salmonella usually causes damage – and the technique could lead to  a highly targeted technique of fighting one of the worst types of cancer there is.

Researchers from Duke University gave the treatment to rats with the aggressive brain cancer glioblastoma, and saw significant increases in lifespans, with 20 percent of the rodents surviving an extra 100 days compared to control animals – the equivalent of 10 years in human terms.

“Since glioblastoma is so aggressive and difficult to treat, any change in the median survival rate is a big deal,” says one of the team, Johnathan Lyon.

“And since few survive a glioblastoma diagnosis indefinitely, a 20 percent effective cure rate is phenomenal and very encouraging.”

salmonella-close-lookBacteria (pink) take hold of cancer cells (blue). Credit: Duke University

It’s a promising direction of study, since survival rates of humans with this cancer are pretty bleak. Only about 30 percent of patients with glioblastoma live for more than two years after diagnosis.

Part of what makes it so hard to treat is that the tumours hide behind the blood-brain barrier, which separates the circulating blood from the brain’s own fluid.

Conventional drugs can’t easily reach through this membrane, so a more targeted approach is needed to stop glioblastoma from thriving.

To achieve this, the researchers used a genetically adjusted and detoxified form of Salmonella typhimurium, modified to be deficient in a crucial organic compound called purine.

Glioblastoma tumours are an abundant source of this enzyme, which induces the bacteria to seek out the cancer cells to get the purine that they need.

And when the bacteria get to the tumours, two more genetic tweaks kick into action.

Because cancerous cells multiply so quickly, oxygen is scarce inside and around tumours. Knowing this, the scientists coded their Salmonella to produce two proteins called Azurin and p53 in the presence of low levels of oxygen.

These compounds instruct the cancer cells to effectively self-destruct, so the end result is like a genetically-coded guided missile, seeking out the tumour and blitzing cancerous cells when it arrives.

The researchers say the technique is much more accurate than surgery, and because the bacteria are otherwise detoxified, there should be no damaging side effects for the patient.

Of course, having success with a group of rats is no guarantee that the treatment will translate to the human body, but the researchers are hopeful that the technique can be developed to treat cancer patients in the future.

The first step is to get that 20 percent success rate up. Based on initial tests, the 80 percent of cases where the treatment had no effect could be down to the tumour cells outpacing the bacteria, or inconsistencies in the Salmonella‘s penetration in the body.

“It might just be a case of needing to monitor the treatment’s progression and provide more doses at crucial points in the cancer’s development,” says Lyon.

“However, this was our first attempt at designing such a therapy, and there is some nuance to the specific model we used, thus more experiments are needed to know for sure.”

The research has been published in Molecular Therapy Oncolytics.

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New treatment based on ocean bacteria shown to stop the spread of prostate cancer

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Scientists just completed a trial of a new, non-surgical prostate cancer treatment that uses a tumour-killing drug based on ocean bacteria, and the procedure saw almost half the patients go into complete remission.

The treatment is known as vascular-targeted photodynamic therapy (VTP), and is made possible by a drug called WST11, which is derived from bacteria that live at the bottom of the ocean. These light-sensitive organisms convert photons into energy, and when the same trick is mimicked by WST11, the compound kills cancer cells.

In a broad clinical trial at 47 treatment sites across 10 different European countries, 49 percent of patients with early prostate cancer that were treated with VTP went into complete remission, compared with 13.5 percent in the control group.

“These results are excellent news for men with early localised prostate cancer, offering a treatment that can kill cancer without removing or destroying the prostate,” says lead researcher Mark Emberton from University College London.

“This is truly a huge leap forward for prostate cancer treatment, which has previously lagged decades behind other solid cancers such as breast cancer.”

Men diagnosed with early or low-risk prostate cancer are usually monitored via regular testing to make sure the cancer isn’t spreading.

But if it does begin to spread, patients face a dilemma, as traditional treatments such as surgery or radiation therapy can cause lifelong erectile problems and incontinence.

For these reasons, a non-surgical treatment that doesn’t come with such negative side effects has long been a goal of researchers, and VTP with WST11 could be it.

In the study, the procedure only caused short-term urinary and erectile problems, which had resolved within three months, and all other side effects disappeared within two years.

“This changes everything,” Emberton told James Gallagher at the BBC.

“Traditionally the decision to have treatment has always been a balance of benefits and harms. … To have a new treatment now that we can administer, to men who are eligible, that is virtually free of those side effects, is truly transformative.”

The treatment involves injecting WST11 into the bloodstream, and inserting optical fibres into the prostate gland.

When the optical fibres are turned on, light beams activate the drug in the patient’s blood, causing it to release high-energy free radicals that destroy tumour tissue while leaving surrounding tissue unharmed.

Of the individuals who took part in the trial, cancer progressed in 58 percent of men in the control group, who maintained regular monitoring during the study. But for the men who received VTP, only 28 percent saw tumours spread.

According to Emberton, these results would be even stronger today, as the researchers in the trial didn’t have access to the latest MRI technology when they began their study in 2011.

“We can now pinpoint prostate cancers using MRI scans and targeted biopsies, allowing a much more targeted approach to diagnosis and treatment,” Emberton said in a press release.

“This means we could accurately identify men who would benefit from VTP and deliver treatment more precisely to the tumour. With such an approach, we should be able to achieve a significantly higher remission rate than in the trial and send nearly all low-risk localised prostate cancers into remission.”

There’s also scope to extend the procedure to other cancers, including breast and liver cancer, but first the researchers need to continue monitoring the patients who took part in this trial and see if the remission rates hold up over time.

Meanwhile, the European Medicines Agency (EMA) is currently reviewing the treatment, but it could be years before it’s made available to patients in the broader population.

It’s important to note that there’s still a lot we don’t know about this treatment, and despite its early promise, it’s not necessarily more effective than surgery or radiation therapy at removing the danger of cancer.

That said, it also doesn’t seem to offer the same kinds of complications, so depending on how further research pans out, it could be a valid avenue of treatment in the future.

One man who hopes the wait isn’t too long is Gerald Capon, a 68-year-old from West Sussex in the UK, who took part in the study.

“[T]he trial changed my life. I’m now cancer-free with no side effects and don’t have to worry about needing surgery in future,” he says.

“I feel so lucky to be in this position… I hope that other patients will be able to benefit from this treatment in future.”

The findings are reported in The Lancet Oncology.

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USFDA permits marketing of new tissue expander for women undergoing breast reconstruction following mastectomy

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The U.S. Food and Drug Administration today allowed marketing of a new tissue expander system for soft tissue expansion in two-stage breast reconstruction following mastectomy and in the treatment of underdeveloped breasts and soft tissue deformities. A patient uses a dose controller to independently inflate the expander.

A tissue expander is a balloon-like device that has a soft, expandable polymer shell and is gradually filled with saline or air. Tissue expanders are typically used prior to breast reconstruction to cause breast tissue and muscle to stretch over time, which creates a space (called a “pocket”) for the breast implant.

The AeroForm device is a wireless tissue expander for patients who choose to have reconstructive surgery following a mastectomy. Most women who have mastectomies to treat or prevent breast cancer are eligible for breast reconstruction.

“This tissue expander may result in fewer office visits for patients by allowing a patient to partially control their breast tissue expansion,” said Binita Ashar, M.D., director of the Division of Surgical Devices at the FDA’s Center for Devices and Radiological Health. “Patients need to speak with their surgeons about what type of tissue expander is appropriate for them and the benefits and risks of using an expander following their mastectomy.”

The AeroForm tissue expander system has two main components: a sterile implant with an outer shell made of silicone (called the “expander”) and a remote dosage controller (called the “controller”). The expander contains a reservoir of compressed carbon dioxide. The controller is a hand-held device that communicates with the receiving antenna and electronics located in the expander. The controller is used to communicate to a valve in the reservoir to release carbon dioxide and gradually inflate the expander. The controller is pre-programed to limit releasing a small amount of carbon dioxide once every three hours, up to a maximum of three times per day.

The AeroForm tissue expander differs from available saline-filled tissue expanders. Saline expanders are expanded by the surgeon and use a needle to pierce the skin and inject saline into the expander through a port or injection area. The AeroForm tissue expander is filled with air; there is no need for a needle and the patient has some control over slowly expanding the device at home.

The FDA reviewed results from a clinical trial of 99 patients using the AeroForm expander and 52 patients using the saline expander. The results showed that 96.1 percent of patients using AeroForm expanders and 98.8 percent of patients using saline expanders were able to have their breast tissue successfully expanded and exchanged to a breast implant.

A surgeon must determine whether the patient is a suitable candidate for treatment with the device. Patients must not have any residual tumor at the expansion site and must not undergo magnetic resonance imaging (MRI) while the device is in place. Patients with another electronic implant (e.g. pacemaker, defibrillator, or neurostimulator device) are not eligible for treatment with the AeroForm tissue expander.

The most common adverse events seen in the study were necrosis, seroma, post-operative wound infection and procedural pain. Patients using the AeroForm device in the clinical trials did not report any serious adverse events.

The FDA reviewed the data for the AeroForm system through the de novo premarket review pathway, a regulatory pathway for some low- to moderate-risk devices that are novel and for which there is no legally marketed predicate device to which to claim substantial equivalence.

AeroForm is manufactured by AirXpanders of Palo Alto, California.

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USFDA reviews Pfizer’s drug for Metastatic Breast Cancer

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Image result for metastatic breast cancer

Pfizer has announced that the FDA accepted for review a supplemental New Drug Application (sNDA) for its first-in-class CDK 4/6 inhibitor, IBRANCE (palbociclib). The sNDA supports the conversion of the accelerated approval of IBRANCE in combination with letrozole to regular approval and includes data from the phase III PALOMA-2 trial, which evaluated IBRANCE as initial therapy in combination with letrozole for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer. This is the same patient population as the randomized phase II PALOMA-1 trial upon which the accelerated approval of IBRANCE plus letrozole was granted in February 2015.

The sNDA was granted Priority Review status, which accelerates FDA review time from 10 months to a goal of six months from the day of acceptance of filing.1 The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in April 2017.

“Since its introduction in 2015, more than 45,000 patients have been prescribed IBRANCE by more than 9,000 providers in the U.S.,” said Liz Barrett, global president and general manager, Pfizer Oncology. “We are pleased that the PALOMA-2 trial has further demonstrated the significant clinical benefit of IBRANCE in the first-line setting, providing additional evidence for its continued use as a standard of care medicine.”

PALOMA-2 is a randomized (2:1), multicenter, double-blind phase III study that evaluated a total of 666 women from 186 global sites in 17 countries. The study demonstrated that IBRANCE in combination with letrozole improved progression-free survival compared to letrozole plus placebo as a first-line treatment for postmenopausal women with ER+, HER2- metastatic breast cancer. The adverse events observed with IBRANCE in combination with letrozole in PALOMA-2 were generally consistent with their respective known adverse event profiles

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We now have more evidence that fat fuels cancer’s spread

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Scientists have found that the cells responsible for spreading cancer around the bodies of mice have a big weakness – they need certain fats to fuel their growth.

Now a team of researchers has shown that by blocking these cells from absorbing fat they can actually stop cancer from metastasising in mice – and they’re hoping the results might help them do the same in humans.

Metastasis is the leading cause of cancer-related deaths in the world, but until now, scientists have struggled to understand exactly how and why cancer cells go through the energy-intensive process of splitting off, travelling through the bloodstream, and taking root somewhere else in the body.

In the past, it was assumed that sugar was cancer’s main fuel source, but a study earlier this year suggested that we’d been looking at metastasis entirely wrong – what if fat was actually driving the spread of cancer?

Now a new study adds more weight to this hypothesis.

A team of researchers identified the cells responsible for the spread of oral cancer in mice, and showed that they rely on fatty acids – including palmitic acid, a major component of common food additive palm oil – to spread around the body.

They figured this out after noticing that many of the metastasising cells expressed high levels of a receptor protein called CD36, which helps cells absorb lipids.

High expression of CD36 has also been linked to poor medical outcomes in cancer patients, so the team decided to see what would happen if the receptor was blocked.

Incredibly, the researchers showed that when they blocked CD36 expression in a range of human cancer cells, they were able to stop the cancer from spreading altogether in mice – although it didn’t stop primary tumours from forming.

“We hypothesise that metastatic cells rely so much on the availability of certain fatty acids, that they cannot cope without them,” lead researcher Salvador Aznar Benitah told Research Gate.

“However, we still do not know the precise mechanism of why blocking CD36 results in such a strong effect on metastasis.”

While the team still has more work to do, their results so far show that the approach might also work after cancer has metastasised.

In mice, blocking CD36 with antibodies eradicated metastatic tumours 15 percent of the time, and the remaining tumours that had spread shrunk by at least 80 percent.

The study also showed that mice fed high-fat diet had more and larger tumours in their lymph nodes and lungs – which is a sign of them spreading – compared to mice on normal diets.

To be clear, this research has only been done on human cancer cells in mice, so there’s no guarantee the same thing will work in human patients.

And at this stage, no one is recommending anyone cut fats from their diets to avoid cancer spread – especially seeing as many cancer patients need high-energy diets in order to stay healthy.

But the team is working on creating antibodies that work against CD36 in humans, and hope to test them in clinical trials within the next five years.

“This is an important and exciting first step,” said Benitah. “Now that we have been able to identify these cells responsible for metastasis, we can study their behaviour in much more detail.”

“Also, it opens the possibility of a new anti-metastatic therapy based on blocking the ability of these cells to uptake fatty acids,” he added.

We’re looking forward to seeing what comes of this research, because while we’re closing in on many revolutionary new treatments for cancer, being able to stop it from spreading in the first place would be incredible.

The research has been published in Nature.

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