Game-changing cancer drugs which can attack all tumours will be fast-tracked by NHS

Game-changing cancer drugs which can attack all types of tumour will be fast-tracked by the NHS, the head of the health service will today announce.

•  Laura Donnelly, health editor

19 JUNE 2019 • 12:01AM

A revolutionary class of treatments could offer hope to thousands of patients in cases which were previously untreatable CREDIT: SCIENCE PHOTO LIBRARY

Simon Stevens will say that a revolutionary class of treatments - known as “tumour agnostic” drugs - could offer hope to thousands of patients in cases which were previously untreatable.

They work by targeting tumours according to their genetic make-up, rather than where they originate in the body.

As a result, they can be used to treat a range of type of diseases - shrinking tumours in up to three quarters of cancers tested.

Today Mr Stevens will tell a conference of NHS leaders in Manchester that preparations are underway to ensure the next generation of treatment can be quickly made available to patients.

Two of the first drugs are expected to be licenced later this year, and could be approved by NHS rationing bodies soon after, depending on price negotiations.

Earlier detection and treatment of cancer is a central part of the long-term plan for the health service.

Mr Stevens is expected to tell the NHS Confederation conference: “This exciting new breakthrough in cancer treatment is the latest example of how the NHS can lead the way in the new era of personalised cancer care.

“The benefits for patients, in particular children, of being able to treat many different types of cancers with one drug is potentially huge, helping them to lead longer, healthier lives.”

It follows a decision last year to make England the first country in Europe to fund another pioneering treatment, called Car-T, which programmes the body to attack rogue cells, for children.

Today Mr Stevens will say that children should also be among the first to benefit from the new generation of drugs, which target tumours with the genetic variation which accelerates growth.

With such treatments, testing the tumour’s genes or other molecular features assists in deciding which treatments may be best, regardless of where the cancer is located.

The advances are possible because of the NHS national genomic medicine and testing service, launched last year, which allows patients to be tested to see who can benefit from access to targeted treatment, often when no other options are available.

The genetic flaw - known as neurotropic tyrosine receptor kinase, or NTRK - is most commonly found in rare cancers such as  salivary tumours and infantile fibrosarcoma but is also in low levels in more common cancers.

Two drugs - Larotrectinib, produced by Bayer, and entrectinib, from Roche, are expected to be the first drugs to be licenced, later this year.

Health officials said around 850 patients a year could benefit from the frontrunners while many thousands a year are eventually expected to benefit from other treatments on the horizon.

The drugs work by blocking the NTRK enzyme, effectively shrinking the tumour. Early clinical trials showed the tumour responded in two thirds to three quarters of the cancers tested.

Existing cancer drugs need to be approved by the National Institute for Health and Care Excellence for each individual type of cancer they treat such as breast or colon cancer.

However, when approved, the new drugs would be available to treat all types of tumour without individual approval.

Mr Stevens will urge health leaders to prepare to introduce the drugs, ahead of meetings next week about how to ensure speedy adoption of the drugs.

Today he will also say that manufacturers need to set fair and affordable prices for the treatments. In recent months, a number of deals have been agreed between the NHS and manufacturers, allowing the rollout of drugs for rare disease, but they remain at loggerheads about the pricing of a treatment for cystic fibrosis, which the NHS refuses to fund.

Mr Stevens will today say: “Preparations are underway to make sure the NHS can adopt these next generation of treatments, but manufacturers need to set fair and affordable prices so treatments can be made available to those who need them.”

https://www.telegraph.co.uk/news/2019/06/18/game-changing-cancer-drugs-can-attack-tumours-will-fast-tracked/

Antitumor immune function in liver and gut microbiome - MUST READ

NCI study finds gut microbiome can control antitumor immune function in liver

• Posted: May 24, 2018

3D illustration of gut bacteria.

Credit: iStock

Healthwise

Scientists have found a connection between bacteria in the gut and antitumor immune responses in the liver. Their study, published online May 24 in Science, was led by researchers in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI). 

It showed that bacteria found in the gut of mice affect the liver’s antitumor immune function. The findings have implications for understanding the mechanisms that lead to liver cancer and for therapeutic approaches to treat them. NCI is part of the National Institutes of Health. 

“What we found using different tumor models is that if you treat mice with antibiotics and thereby deplete certain bacteria, you can change the composition of immune cells of the liver, affecting tumor growth in the liver,” said Tim Greten, M.D., of NCI’s CCR, who led the study. “This is a great example of how what we learn from basic research can give us insight into cancer and possible treatments.” 

The microbiome is the collection of bacteria and other microorganisms that live in or on the body. In humans, the greatest proportion of the body’s total microbiome is in the gut. Despite extensive research into the relationship between the gut microbiome and cancer, the role of gut bacteria in the formation of liver cancer has remained poorly understood. 

To investigate whether gut bacteria affect the development of tumors in the liver, Dr. Greten and his team carried out a series of experiments with mice. They used three mouse models of liver cancer, and found that when they depleted gut bacteria using an antibiotic “cocktail,” the mice that had the antibiotics developed fewer and smaller liver tumors and had reduced metastasis to the liver.

The investigators next studied the immune cells in the liver to understand how the depletion of gut bacteria suppressed tumor growth in the liver of the antibiotic-treated mice. Antibiotic treatment increased the numbers of a type of immune cell called NKT cells in the livers of the mice. Further experiments showed that, in all three mouse models, the reduction in liver tumor growth that resulted from antibiotic treatment was dependent on these NKT cells. Next, they found that the accumulation of the NKT cells in the liver resulted from an increase in the expression of a protein called CXCL16 on cells that line the inside of capillaries in the liver.

“We asked ourselves, why do mice treated with antibiotics have more CXCL16 production in these endothelial cells?” Dr. Greten said. “That was the critical point, when we found that bile acids can control the expression of CXCL16. We then did further studies, and found that if we treat mice with bile acids, we can actually change the number of NKT cells in the liver, and thereby the number of tumors in the liver.”

Bile acids are formed in the liver and help break down fats during digestion.

Finally, the investigators found that one bacterial species, Clostridium scindens, controls metabolism of bile acids in the mouse gut—and ultimately CXCL16 expression, NKT cell accumulation, and tumor growth in the liver.

Dr. Greten explained that while many studies have shown an association between gut bacteria and immune response, this study is significant in that it identifies not just a correlation, but a complete mechanism of how bacteria affect the immune response in liver. In the same study, the researchers found that bile acids also control the expression of the CXCL16 protein in the liver of humans and wrote that, though these results are preliminary, the novel mechanism described in this study could potentially apply to cancer patients. 

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process—each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research. 

About the Center for Cancer Research (CCR): CCR comprises nearly 250 teams conducting basic, translational, and clinical research in the NCI intramural program—an environment supporting innovative science aimed at improving human health. CCR’s clinical program is housed at the NIH Clinical Center—the world’s largest hospital dedicated to clinical research. For more information about CCR and its programs, visit ccr.cancer.gov. 

About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s Contact Center (formerly known as the Cancer Information Service) at 1-800-4-CANCER (1-800-422-6237). 

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.gov.

Reference

1. Ma C, Han M, Heinrich B, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science. May 25, 2018. DOI: 10.1126/science.aan5931

“NCI study finds gut microbiome can control antitumor immune function in liver was originally published by the National Cancer Institute.”

Healthwise

https://www.cancer.gov/news-events/press-releases/2018/gut-microbiome-liver-cancer

Chemotherapy before breast cancer surgery might fuel metastasis

W

hen breast cancer patients get chemotherapy before surgery to remove their tumor, it can make remaining malignant cells spread to distant sites, resulting in incurable metastatic cancer, scientists reported last week.

By SHARON BEGLEY @sxbegle

JULY 10, 2017

A breast cancer tumor imaged with a technique that highlights aspects of its microenvironment.NATIONAL CANCER INSTITUTE/UNIV. OF CHICAGO COMPREHENSIVE CANCER CENTER

The main goal of pre-operative (neoadjuvant) chemotherapy for breast cancer is to shrink tumors so women can have a lumpectomy rather than a more invasive mastectomy. It was therefore initially used only on large tumors after being introduced about 25 years ago. But as fewer and fewer women were diagnosed with large breast tumors, pre-op chemo began to be used in patients with smaller cancers, too, in the hope that it would extend survival.

But pre-op chemo can, instead, promote metastasis, scientists concluded from experiments in lab mice and human tissue, published in Science Translational Medicine.

The reason is that standard pre-op chemotherapies for breast cancer — paclitaxel, doxorubicin, and cyclophosphamide — affect the body’s on-ramps to the highways of metastasis, said biologist John Condeelis of Albert Einstein College of Medicine, senior author of the new study.

Called “tumor microenvironments of metastasis,” these on-ramps are sites on blood vessels that special immune cells flock to. If the immune cells hook up with a tumor cell, they usher it into a blood vessel like a Lyft picking up a passenger. Since blood vessels are the highways to distant organs, the result is metastasis, or the spread of cancer to far-flung sites.

Depending on characteristics such as how many tumor cells, blood vessel cells, and immune cells are touching each other, the tumor microenvironment can nearly triple the chance that a common type of breast cancer (estrogen-receptor positive/HER2 negative) that has reached the lymph nodes will also metastasize, Condeelis and colleagues showed in a 2014 study of 3,760 patients. The discovery of how the tumor microenvironment can fuel metastasis by whisking cancer cells into blood vessels so impressed Dr. Francis Collins, director of the National Institutes of Health, that he featured it in his blog.

The new study took the next logical step: Can the tumor microenvironment be altered so that it promotes or thwarts metastasis?

To find out, Einstein’s George Karagiannis spent nearly three years experimenting with lab mice whose genetic mutations make them spontaneously develop breast cancer, as well as mice given human breast tumors. In both cases, paclitaxel changed the tumor microenvironments in three ways, all more conducive to metastasis: The microenvironment had more of the immune cells that carry cancer cells into blood vessels, it developed blood vessels that were more permeable to cancer cells, and the tumor cells became more mobile, practically bounding into those molecular Lyfts.

As a result, the mice had twice as many cancer cells zipping through their bloodstream and in their lungs compared with mice not treated with paclitaxel. Two other neoadjuvants, doxorubicin and cyclophosphamide, also promoted metastasis by altering the tumor microenvironment. “This showed that the tumor microenvironment is the doorway to metastasis,” Condeelis said.

The scientists also analyzed tissue from 20 breast cancer patients who had undergone pre-op chemo (12 weeks of paclitaxel and four of doxorubicin and cyclophosphamide). Compared to before the chemo, the tumor microenvironment after treatment was more conducive to metastasis in most patients. In five, it got more than five times worse. No patient’s microenvironment got less friendly to metastasis.

Pre-op chemo “may have unwanted long-term consequences in some breast cancer patients,” the Einstein researchers wrote.

That finding is “fascinating, powerful, and very important,” said Julio Aguirre-Ghiso, of Mount Sinai School of Medicine, an expert in metastasis who was not involved in the study. “It raises awareness that we might have to be smarter about how we use chemotherapy.”

Dr. Julie Gralow, a medical oncologist at the University of Washington, said that if pre-op chemo promoted metastasis, that should have shown up in studies that compared it to post-op chemo, but for the most part it hasn’t. However, that could be because only tumor cells containing certain proteins that make them especially mobile are affected in this way. “This is an interesting study, to say the least,” Gralow said. “I am willing to keep my mind open to the possibility that there are some breast cancer patients in whom things get worse” with pre-op chemo.

One reason to question the findings, however, is that if pre-op chemo promotes metastasis in some patients, that might be expected to have shown up in studies of the therapy. Overall, in fact, those studies show that “neoadjuvant chemotherapy does not seem to improve overall survival,” as the authors of an editorial in the Journal of Clinical Oncology wrote.

That’s not as bad as decreasing survival, of course. But Einstein’s Dr. Maja Oktay, a co-author of the new research, cautioned that the typical length of the studies — six or so years — is too short to assess the risk of metastasis, “which can take more than 20 years” to appear, she said. Such patients might never be flagged as having metastatic cancer, let alone having it linked to pre-op chemo decades earlier, said Aguirre-Ghiso.

On a brighter note, not all breast cancer patients have the kind of tumor microenvironment in which pre-op chemo can promote metastasis. Whether they do or not can be determined by a simple lab test, but one that is not routinely done, Condeelis said.

Serendipitously, an experimental compound called rebastinib, being developed by Deciphera Pharmaceuticals, seems to be able to block the on-ramp to the metastasis highway. In a study currently recruiting patient volunteers, the Einstein scientists (who have no financial relationship with Deciphera) are studying whether rebastinib can improve outcomes in metastatic breast cancer.

https://www.statnews.com/2017/07/10/breast-cancer-chemotherapy/

Antifungal drug kills dormant colorectal cancer cells

Colorectal cancer is the fourth most commonly diagnosed type of cancer in the United States. Though various treatments are available for it, certain tumor cells are therapy-resistant. Now, research suggests that an antifungal drug may be effective against these persistent cells.

 Published Sunday 3 June 2018

By Maria Cohut

Fact checked by Jasmin Collier

Can itraconazole, an antifungal drug, eliminate therapy-resistant cancer cells and halt tumor progression?

The drug itraconazole is typically used in the treatment of fungal infections.

These can include certain types of vaginal yeast (vulvovaginal candidiasis) and fungal infections on the hands and feet (Tinea pedis and Tinea manuum).

But researchers from the Cancer Research UK Cambridge Institute have suggested a brand new use for this substance — namely, as a treatment that is able to eliminate dormant tumor cells in colorectal cancer.

This is one of the most common cancer types in the U.S., and an estimated 140,250 people will learn that they have this disease in 2018, according to the National Cancer Institute (NCI).

"One of the biggest challenges in treating any cancer is the diversity of different cells within the same tumor," explains co-lead author Dr. Simon Buczacki, who participated in the new study investigating the effect of itraconazole on dormant colorectal cancer cells.

In this study, he continues, the team "targeted a type of cell that lies asleep within bowel tumors, remaining unresponsive to treatment and putting the patient at risk of their cancer coming back."

In experiments conducted on mice, Dr. Buczacki and team found that the antifungal drug may be able to trigger the death of a type of colorectal cancer cell typically immune to treatment.

These tumor cells are found in a state of inactivity, or "dormancy," so they do not respond to the usual therapies, such as chemotherapy, that target and destroy active cancer cells.

So, even as a treatment is effective in destroying most malignant cells, these dormant units will remain unaffected, putting the person at risk of having a recurrence of the cancer later on.

Itraconazole halts tumor progression

In the study — the findings of which have been published in the Journal of Experimental Medicine— the researchers worked with cancer tumors grown in mice models of colorectal cancer.

First of all, they focused on identifying which signaling pathways were involved in controlling cell dormancy in the case of cancer tumors. They saw that, for colorectal cancer, there are two: Wnt and "hedgehog" pathways.

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Then, they tested the effectiveness of various drugs on these two pathways, and it was then that they noticed itraconazole's therapeutic potential.

Dr. Buczacki and team discovered that itraconazole interfered with the Wnt pathway, which led to the elimination of the dormant cells and blocked the growth of the cancer tumor.

"What's interesting is that this drug seems to kick both dormant and non-dormant cells into action," notes Dr. Buczacki.

"It forces cells back into a short cycle of growth," he explains, "before slamming on an irreversible 'stop' button, entering a permanent standstill that's known as senescence."

Following these promising results, the team would eventually like to test the effectiveness of this drug in clinical trials, on patients with colorectal cancer at an advanced stage.

Another step would be to ascertain whether itraconazole would be more effective on its own, or used in combination therapy, administered alongside other drugs.

Prof. Greg Hannon — the director of the Cancer Research UK Cambridge Institute — comments on the discovery, calling the research an "innovative study" that "has taken a step toward addressing one of the biggest challenges in cancer research."

"The presence of drug-resistant, dormant tumor cells is a problem in many types of cancer," he says.

"If we find ways to target these cells in bowel cancer, it might provide insights into tackling the problem of dormant tumor cells more broadly."

Prof. Greg Hannon

https://www.medicalnewstoday.com/articles/322009.php

‘Holy grail’ of blood tests can detect 10 types of cancer

Doctors could soon be able to detect 10 different types of cancer using a simple blood test.

The “holy grail” of cancer tests could pave the way for a universal screening program that could save tens of thousands of lives each year.

By James Jackson, The Sun

June 1, 2018

Experts say the simple check allows early diagnosis when survival chances are higher.

It works by pinpointing DNA that has broken free of a tumor.

The test was administered on 749 cancer-free patients and 878 with newly diagnosed but untreated cancer.

It can currently detect ovarian, pancreatic, liver, lymphoma, multiple myeloma, colorectal, esophageal, lung, head and neck, and breast cancers, but it works best for ovarian and pancreatic forms of the disease.

The “comprehensive” test identified 90 percent of ovarian cancers and 80 percent of pancreatic and liver cancers.

It picked out four in five liver tumors, 58 percent of breast cancers and 59 percent of lung cancers.

Experts say it could be available in hospitals within a few years and is likely to cost between $660 and $1,300 each time.

Study leader Dr. Eric Klein from the Cleveland Clinic, said: “This blood test detected multiple cancers at various stages with high specificity, indicating this approach is promising as a multi-cancer screening test.

“It gives us the opportunity to find cancers months or years before someone would develop symptoms and be diagnosed.

“It is potentially the Holy Grail of cancer research – to find cancers that are currently hard to cure at an earlier stage when they are easier to cure.

“This test could be used for everybody, regardless of their family history.

“More research is needed but it could be given to healthy adults of a certain age, such as those over 40, to see if they have early signs of cancer.”

Professor Nicholas Turner, from the Institute of Cancer Research, London, described the findings as “really exciting.”

“Far too many cancers are picked up too late, when it is no longer possible to operate and the chances of survival and slim,” he said.

“The goal is to develop a blood test, such as this one, that can accurately identify cancers in their earliest stages.

“This particular test is really exciting but it is likely to be a few years before it is ready for clinical use.

“When this test, or another like it, are ready for clinical use, it could be used as part of a universal screening program, with the potential to save many lives.”

Fiona Osgun, from Cancer Research UK, added: “The idea that we could one day offer people a blood test that could find cancer earlier is certainly exciting.

“Detecting cancer early, before it has spread is one of the most powerful ways to ensure more people are offered treatments which give them a better chance of beating the disease.”

Simon Stevens, chief executive of the National Health Service in England, said: “We stand on the cusp of a new era of personalized medicine that will dramatically transform care for cancer and for inherited and rare diseases.

“In particular, new techniques for precision early diagnosis would unlock enormous survival gains, as well as dramatic productivity benefits in the practice of medicine.”

The findings were presented at the annual conference of the American Society of Clinical Oncology in Chicago.

https://nypost.com/2018/06/01/holy-grail-of-blood-tests-can-detect-10-types-of-cancer/

New breast cancer blood test could improve treatment options in more serious cases

'Liquid biopsy' detects tumour DNA and can track alterations in 13 different genes

Women with advanced stages of breast cancer could receive potentially life-extending personalised treatment after taking a new blood test that detects tumour DNA.

The test, known as a “liquid biopsy”, can detect and track alterations in 13 different genes, including some of the most important drivers of the disease.


A doctor examines a mammograph of a breast cancer patient Rex Features

• Thursday 27 July 2017

Breast cancer is the most common type of cancer in the UK, with around 150 new cases diagnosed every day. 

For patients whose cancer has spread beyond the breast and nearby glands – the most deadly stage of the disease – the new test could be used to improve and individualise their treatment as the disease progresses, researchers have said.

Around 10 per cent of women have metastatic, or stage four, breast cancer at the time of their diagnosis, according to cancer support charity Macmillan. The average survival rate is around two years.

This is the first time scientists have been able to analyse two kinds of acquired DNA mutation in a single blood test.

The study, published in the journal Clinical Chemistry, described how the researchers first looked at cells grown in a laboratory before analysing DNA in blood donated by 42 women with advanced breast cancer.

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Cancer-specific genetic changes were detected in half the women. In the case of one in five patients, information from the tumour DNA could have been used to alter treatment.

None of the mutations were found in the blood of nine healthy women that was also tested.

One gene that can be examined for changes using the new blood test is called HER2. It usually makes proteins that control the growth of healthy breast cells, but also plays a role in the development of around 15 to 25 per cent of breast cancer cases.

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These “HER2 positive” breast cancers can be targeted with the drug Herceptin.

In addition, the test can spot mutations in the oestrogen receptor gene ESR1, linked to resistance to anti-hormone therapies such as aromatase inhibitors.

Once a patient is known to have these mutations, she can be offered other forms of treatment such as chemotherapy.

“By analysing blood plasma to measure for cancer-specific changes to key breast cancer genes – including the HER2 and oestrogen receptor genes – we hope this test could help doctors and patients choose the best treatment at the best time,” said Dr David Guttery, from the University of Leicester.

Somatic “point” mutations occur when DNA molecules are shuffled in the wrong order. Copy number alterations (CNA) are another type of mutation involving extra copies of genes that produce too much protein.

“We have developed a novel blood test that can simultaneously detect somatic mutations and copy number alterations that are integral in driving the growth of breast cancer,” said Dr Guttery.

“This study represents proof of concept, and further validation is now needed to confirm the clinical usefulness of this test before any test could be rolled out.”

The study was funded by two charities, Breast Cancer Now and Cancer Research UK.

Baroness Delyth Morgan, chief executive of Breast Cancer Now, said: “If validated by further research, this blood test could help tell us how a patient's secondary breast cancer is evolving. 

“Analysing the genetic make-up of tumours could enable us to identify women who might benefit from changing their treatment, ensuring that breast cancer patients receive the most personalised therapy possible.“

Dr Justine Alford, senior science information officer at Cancer Research UK, said: “While survival for women with early breast cancer has greatly improved, the outlook for patients with advanced disease is still poor, something we urgently need to change. This early research could help achieve this.

“The researchers may have developed a way to track breast cancer as it grows, allowing doctors to act swiftly and give patients the treatments that are right for them as early as possible. On top of that, such a tailored approach could spare patients receiving drugs, and the side effects that go with them, that aren't likely to work.”

http://www.independent.co.uk/news/health/breast-cancer-blood-test-new-treatment-improve-detect-tumour-dna-liverpool-uk-advanced-metastatic-a7862241.html