Oxford University scientist developing new treatments to tackle breast cancer that has spread to the brain

Oxford University scientist developing new treatments to tackle breast cancer that has spread to the brain
Professor Nicola Sibson of the Department of Oncology has been awarded a grant worth almost £200,000 by research charity Breast Cancer Now to fund cutting-edge research to uncover novel treatment combinations to control breast cancer that has spread to the brain.
The news comes on Secondary Breast Cancer Awareness Day (Friday 13th October 2017), as leading charity Breast Cancer Now announces more than £700,000 of funding across the UK for research specifically targeting secondary (or metastatic) breast cancer – where the disease has spread to another part of the body.
When breast cancer spreads, known as secondary or metastatic breast cancer, it becomes incurable. While metastatic breast cancer can sometimes be controlled using different combinations of treatments, it cannot be cured, and almost all of the 11,500 women that die as a result of breast cancer each year in the UK will have seen their cancer spread. Nearly 600 women in Oxfordshire are diagnosed with breast cancer every year, and over 100 women in the region die from the disease each year.1
The brain is protected by its own security system, a structure called the blood-brain barrier (BBB). The BBB acts as a filter, preventing harmful substances from reaching the brain. However the virtually impenetrable nature of the BBB makes delivery of drugs to the brain extremely difficult, meaning there are few effective treatments for breast tumours that have spread to the brain (brain metastases).
Up to a third of patients with secondary breast cancer have seen their cancer spread to the brain. This can cause varying problems with brain function depending on which areas the breast cancer cells have spread to, and can often severely affect a patient’s quality of life, with debilitating symptoms such as changes in mood or behaviour, seizures, headaches, vomiting and uncoordinated movement.
Professor Sibson, Professor of Imaging Neuroscience at the CRUK/MRC Oxford Institute for Radiation Oncology has previously found that one element of the immune system, the inflammatory response, is important in the spread of breast cancer to the brain. Her team has previously found that certain inflammatory molecules are present at higher levels in brain metastases, and may be key drivers of tumour growth.
With funding from Breast Cancer Now, Professor Sibson and her team will undertake a three-year project to pinpoint which combinations of anti-inflammatory drugs, which are able to cross the BBB, reduce the growth of breast tumours in the brain most effectively, and whether these could also be given alongside radiotherapy with greater effect.
Professor Sibson said “We urgently need to find ways to treat brain metastases more effectively and improve survival rates. With this funding from Breast Cancer Now our aim is to increase treatment options for patients suffering metastatic spread to the brain. We hope that by targeting the innate immune system we can halt or reduce tumour growth, and enhance the effectiveness of radiotherapy.”
The scientists will first implant breast tumours into the brains of mice, before testing a range of anti-inflammatory drugs and examining the effect on tumour growth. The team will then combine the most effective anti-inflammatories with radiotherapy in mice to identify which combinations best control tumour growth in the brain. The researchers hope to identify new ways to predict which patients are most likely to benefit from anti-inflammatory drugs and radiotherapy. In addition, the team will explore how another component of the inflammatory response, adhesion molecules, are involved in tumour growth, and whether targeting these directly could also be an effective treatment strategy.
Dr Richard Berks, Senior Research Communications Officer at Breast Cancer Now said “Professor Sibson’s research could pave the way for new treatment combinations that could halt tumour growth in men and women whose breast cancers have sadly spread to the brain. Anti-inflammatory drugs are already used to treat arthritis – and if these new combinations are found to be effective, these drugs could be made available for treating patients with brain metastases much more quickly.
“It is essential that we find new ways to treat secondary breast cancer in the brain – to improve quality of life and chances of survival for those living with this debilitating disease.
“Our ambition is that by 2050, everyone who develops breast cancer will live. But if we are to achieve this, we desperately need to raise funds for research to find ways to stop the disease spreading. Professor Sibson’s project could help bring us one step closer to our 2050 vision and we’d like to thank our supporters across Oxford who continue to help make our world-class research possible.” 
Fiona Leslie, 49 from Aylesbury, is living with incurable metastatic breast cancer. Having first been diagnosed with breast cancer in 2013, Fiona underwent a mastectomy, radiotherapy and chemotherapy, before learning that her breast cancer had unfortunately spread to her lungs and her spine.
In April 2015, Fiona began receiving revolutionary drug Kadcyla, which kept her disease at bay for over two years, and enabled her to live a relatively normal life in the meantime. However in June 2017, scans showed that Fiona’s breast cancer had spread to her brain.
1. Local incidence and mortality survival statistics were provided on request by Public Health England, April 2017.

John Findlay wins Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) Prize

The CRUK Oxford Centre is delighted to announce that the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) recently awarded Centre member, John Findlay, its prestigious British Journal of Surgery prize for the best free paper presented at the 2017 AUGIS Scientific Meeting in Cork, Ireland. John is a Specialty Registrar in General Surgery in the Oxford Deanery, and a Senior Clinical Research Fellow in OesophagoGastric Surgery informatics at the NIHR Oxford Biomedical Research Centre.
The prize was awarded for his paper ’Staging gastric cancer with 18F-FDG PET-CT identifies frequent unsuspected metastases and patients of high risk of incurable disease, early recurrence and death’.
This study included 279 consecutive patients with stomach cancer (non-junctional gastric adenocarcinoma) who as part of their treatment at Oxford University Hospitals NHS Foundation Trust underwent a staging PET-CT scan. At present, there is little evidence that routinely using PET-CT in this context is useful. Consequently, it is not recommended by national and international guidelines. However, the Oxford OesophagoGastric Centre has routinely used cutting edge 18F-FDG PET-CT scanning technology for both oesophageal (gullet) and stomach cancer for more than 10 years. The test uses radio-labelled glucose molecules, which tend to concentrate in cancer tissues. These tissues then become visible, or ‘avid’, on the scan and may help provide information about the behaviour of cancer.
In the largest and most contemporary series to date, PET-CT was shown to detect incurable or metastatic cancer in approximately 7% of patients, despite their preceding CT scan being clear. Furthermore, the subgroup of patients who also had avid lymph nodes appeared to be at increased of such incurable disease, and also early cancer recurrence and death after surgery. This builds on previous findings from John’s research in oesophageal and gastro-oesophageal junctional cancer, and suggests PET-CT should also be considered routinely for patients with gastric cancer.
John is now exploring whether PET-CT should also be repeated before surgery if patients receive chemotherapy, and whether the response of avid nodes to this chemotherapy allows clinicians to monitor its effectiveness. He commented that he was honoured to receive this prize on behalf of his collaborators, and hopes that these findings will be able to improve staging and counselling for patients with stomach cancer, and also help identify patients who might benefit from additional investigations.

From bench to bedside in two years: collaborative science opens the way for a new drug for bowel cancer patients across the UK

Today a new drug will become available for patients with bowel cancer as part of a national clinical trial; based on a scientific discovery made only two years ago at the University of Oxford. A yeast genetics research group led by Professor Tim Humphrey in Oxford discovered an Achilles heel of certain cancer cells – mutations in a gene called SETD2. Prof Humphrey and his team showed that cancer cells with a mutated SETD2 gene were killed by an experimental drug being developed by Astra Zeneca called AZD1775 which inhibits a protein called WEE1. WEE1 was first discovered by British Nobel Prize winner Sir Paul Nurse.

The new research by the Humphrey group is exploiting the concept of ‘synthetic lethality’, in which a combination of two factors specifically kills cancer cells, and has the potential to be less toxic and more effective than existing treatments. Collaborating with Dr Andy Ryan’s group in Oxford, the two labs developed a test which would work in human cells to identify the presence or absence of SETD2. They found that about 1 in 10 bowel cancers and up to 50% of kidney cancers lose this marker and so have this susceptibility to being targeted with the drug. The mechanism of activity and the marker which identified the susceptible cells was published in Cancer Cell in November 2015.

The translational potential of this research was quickly developed by the CRUK/MRC Oxford Institute for Radiation Oncology, where clinical and basic scientists worked together with scientists at AstraZeneca to rapidly move the discovery towards a clinical trial. The existing national FOCUS4 trial for patients with bowel cancer provided an opportunity to get this exciting science tested clinically. Today the FOCUS4-C trial, which is open in 100 hospitals across the UK, and coordinated by the Medical Research Council (MRC) Clinical Trials Unit at University College London, will commence this new study.

For patients whose tumours lack a special histone marker, they will be eligible to enter a new part of the study testing the WEE1 inhibitor AZD1775. Patients who have bowel cancer which has spread to other organs and are inoperable can also be registered for the FOCUS4 trial during the initial 12 weeks of their first line treatment and have their tumour tested. The drug is not available except through ethically approved clinical trials.

Professor Tim Maughan, Chief Investigator of FOCUS4, from the CRUK/MRC Oxford Institute for Radiation Oncology, said: “We are very excited that we are able to test this very new approach to treatment for our bowel cancer patients. It is remarkable to be able to take a discovery in yeast cells through to opening a clinical trial on that evidence in less than 2 years. FOCUS4 was designed with this ability to move forward rapidly with new discoveries and test them in patients whose tumours express the characteristics which are predicted to make them sensitive to the new treatment. I am very hopeful this will bring benefit to our patients with bowel cancer.”

Professor Matt Seymour, one of the FOCUS4 clinical investigators and lead for cancer in the National Institute for Health Research Clinical Research Network, said: “What we are seeing here is seamless cooperation between highest-level university science, a major UK-based company, charity, the NHS and our world-leading government-supported clinical research infrastructure. This is UK medical science at its best and most efficient, and a great example of how our joined-up approach can drive exciting inventions rapidly though to clinical research with the potential to benefit NHS patients.”

Professor Tim Humphrey, Senior Group Leader in the CRUK/MRC Oxford Institute for Radiation Oncology, said: “We are excited to have discovered a new way to specifically kill bowel cancer cells with this mutation. To see our work in yeast potentially make a difference to patients in the clinic is very encouraging and shows the value of working together in a larger team of scientists within an Institute.”

Image showing kidney cancer cells before and after treatment with AZD1775, copyright CRUK/MRC Oxford Institute for Radiation Oncology

Dr Anderson Ryan, Senior Group Leader in the CRUK/MRC Oxford Institute for Radiation Oncology, said: “We’re now in the era of precision medicine and patients hope that new treatments will be targeted to their particular disease. This biomarker-driven trial aims to do just that – by using the molecular characteristics of tumours to decide which treatment to offer.”
Malcolm Pope, a former bowel cancer patient, commented: “As a patient, who was fortunate enough to be enrolled on a trial and given new treatment which worked for me, I feel that the progress being made in the Focus4 Trial regarding personalised cancer medicine is both exciting and greatly beneficial for today’s patients.”

Dr Áine McCarthy, Cancer Research UK’s senior science information officer, said: “Developing new targeted treatments for people with bowel cancer is essential to improve survival. Excitingly, these scientists have identified one such potential new treatment which will now be tested in a clinical trial to see if it can be used to treat bowel cancer. This work highlights the importance of carrying out clinical trials like FOCUS4 that can be adapted so that new drugs can be tested quickly, helping patients benefit from these drugs sooner.”

Researchers Make Breakthrough Discovery in Fight against Colorectal Cancer

New research led by Queen’s University Belfast in collaboration with the University of Oxford, has discovered how a genomic approach to understanding colorectal cancer could improve the prognosis and quality of life for patients.

For clinicians, treating patients with bowel cancer can be particularly challenging. Professor Mark Lawler, Chair in Translational Genomics, Centre for Cancer Research and Cell Biology at Queen’s and joint Senior Author on the study explains: “Currently patients with colorectal cancer are offered chemotherapy treatment. While this treatment may be successful for some patients, for others it will have no effect on fighting the cancer, though the patients may suffer debilitating side effects such as nerve damage that can result in a loss of sensation or movement in a part of the body. A ‘one size fits all’ approach isn’t a viable option if we are to effectively tackle this disease.

Researchers from Queen’s, the University of Oxford and the University of Leeds have made a significant advance in the treatment of bowel cancer. The study, which has been published in the high impact journal Nature Communications, has shown how defining precise gene signatures within bowel cancer cells can allow us to develop novel prognostic and predictive markers for bowel cancer and help to drive personalised medicine approaches.

Dr Philip Dunne, Senior Research Fellow at Queen’s said: “Through analysing the molecular and genetic data generated from patient tissue samples, we have discovered that there are different subtypes of bowel cancer. This research unequivocally identifies robust gene signatures that can be used to inform patient management. It will allow us to identify particular gene signatures that indicate sensitivity or resistance to specific therapies. Thus, we can tailor treatment to the individual patient, maximising its effectiveness while minimising potential side effects.”

Professor Tim Maughan, Professor of Clinical Oncology at the University of Oxford and Principal Lead of the S:CORT Consortium said: “This research emphasises how a collaborative approach can give significant insight into bowel cancer disease biology, but also to begin to translate this knowledge into clinically-relevant applications. As part of the work of the S:CORT consortium, we will now focus on making sure that the research is put into practice so that it can become part of the standard of care for patients.”

Bowel cancer is the fourth most common cancer in the UK, with over 41,200 people newly diagnosed each year. A number of treatment options are available but mortality rates remain high, with bowel cancer the second most common cause of cancer death in the UK.

Dr Catherine Pickworth, science information officer at Cancer Research UK, a funder of the study, added: “Personalised medicine aims to give the best treatment to each patient, sparing people unnecessary therapy if it won’t help. This study is a step forward in achieving this, giving us genetic signatures to look out for in bowel cancer patients. The next steps will be to find out which treatment works best for each genetic signatures so that cancer treatments can be tailored to each patient, so they have the best chance of beating cancer.”

This research was performed as part of Stratified Medicine in Colorectal Cancer (S:CORT), an MRC-CRUK funded stratified medicine consortium, bringing together the best of UK science and clinical care in bowel cancer to develop personalised medicine treatment approaches in this common malignancy.

S:CORT involves key partnerships with patients and patient advocacy groups. Ed Goodall, a survivor of bowel cancer and a member of S:CORT explains: “In the past, a tumour was a tumour. Patients are offered chemotherapy and this may not be effective or necessary depending on the patient yet they will still endure all the horrors this treatment can cause including nausea and hair loss. If the oncologist knows more about the subtype of bowel cancer, they will know whether the treatment will be necessary or effective. From a patient point of view, discovering the subtypes of this cancer is really ground breaking work because it will have massive implications for patient care and treatment.”

Deborah Alsina MBE, Chief Executive of Bowel Cancer UK, the UK’s leading bowel cancer research charity and a partner in S:CORT said: “This important study highlights how increasing our understanding of what makes normal cells go wrong is key to developing new approaches that can improve outcomes for patients. With over 16,000 people dying from bowel cancer each year, it is essential that we increase our understanding of what drives the disease and then improve and extend the range of treatment options available. The results of this study take us a step closer to achieving this.”


Dunne, P. D. et al. Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification. Nat. Commun. 8, 15657 doi: 10.1038/ncomms15657 (2017).

 

FOXFIRE Combined Analysis Update

FOXFIRE Combined Analysis indicates no benefit in overall survival from adding selective internal radiotherapy [SIRT] to first-line oxaliplatin-based chemotherapy for metastatic colorectal cancer

Secondary analyses confirm improved control of liver metastases with liver-directed SIRT and show clinical benefit in patients with liver metastases originating from difficult-to-treat right-sided colon cancer

The FOXFIRE Combined Analysis was a study of 1,103 patients randomised to receive either standard first-line chemotherapy for colorectal cancer that has spread to the liver, or the same chemotherapy plus a treatment procedure called selective internal radiotherapy using radioactive yttrium-90 resin microspheres. The primary analysis of this study, which combines data from the SIRFLOX study first presented in 2015 with data from two new studies – FOXFIRE and FOXFIRE-Global – was published today as an abstract by the American Society of Clinical Oncology; it demonstrates no difference in overall survival between patients treated with microspheres plus chemotherapy compared to patients treated with chemotherapy alone.

Colorectal cancer is the fourth most frequently diagnosed cancer worldwide, and the third leading cause of cancer deaths, taking almost 700,000 lives annually. More than half of all patients with colorectal cancer will be diagnosed with metastases, most commonly in the liver.

In the FOXFIRE Combined Analysis, patients in one arm of the study received oxaliplatin-based chemotherapy (mFOLFOX6 or OxMdG), either with or without a biologically targeted agent. In the other arm of the study, patients received the same systemic therapy (with a dose modification of oxaliplatin), plus a single treatment with radioactive yttrium-90 resin microspheres. In order to enter the study, patients were permitted to have a limited number of metastases outside the liver in addition to having metastases in the liver that could not be surgically removed.

More detailed analysis of different patient groups within the study has suggested that the survival of patients with bowel cancer that originates within the right side of the bowel may benefit significantly more from the addition of SIRT using Y-90 resin microspheres to chemotherapy, compared to other patients. The validity of this finding is currently being analysed using data from other clinical studies.

The FOXFIRE Combined Analysis also confirmed that progression-free survival in the liver was significantly longer and that the tumour response was increased in SIRT-treated patients, which correlate with the results of the SIRFLOX study presented in 2015.

The FOXFIRE study was funded by the Bobby Moore Fund of Cancer Research UK and by Sirtex Medical. The study sponsor is the University of Oxford.

Full details of the FOXFIRE Combined Analysis will be presented by Professor Ricky Sharma at the American Society of Clinical Oncology Annual Meeting in Chicago, USA, on 5th June 2017.

New Era in Precision Medicine for Pancreatic Cancer

The development of new treatments for pancreatic cancer is set to be transformed by a network of clinical trials, aiming to find the right trial for the right patient, after a £10 million investment from Cancer Research UK today.

The investment will support the PRECISION Panc project which aims to develop personalised treatments for pancreatic cancer patients, improving the options and outcomes for a disease where survival rates have remained stubbornly low.

A team of researchers from across the UK, including Oxford Centre member Dr Eric O’Neill, aim to speed up recruitment and enrolment of pancreatic cancer patients to clinical trials that are right for the individual patient.

Dr Eric O’Neill said: “the overall goal for PRECISION Panc is to personalise cancer treatment for Pancreatic cancer patients based on their particular genomic background. Oxfords role is to assess whether radiotherapy offers a therapeutic advantage to molecularly targeted approaches for some of the more common pancreatic cancer subtypes. We will be working closely with our partners in PRECISION Panc to ensure findings are expedited into clinical trials to bring advantages to patients as soon as possible”

The researchers will use the molecular profile of each individual cancer to offer patients and their doctor a menu of trials that might benefit them. The first wave of research will establish the best way to collect and profile patient tissue samples. Each patient will have up to five samples taken from their tumour at diagnosis for analysis at the University of Glasgow. The results will guide clinical trial options in the future.

The three trials planned as part of this initiative will recruit a total of 658 patients from a number of centres across the UK – with the scope to add more trials in the future. Patients may also be helped onto suitable clinical trials that are already up and running.

Professor Andrew Biankin, a Cancer Research UK pancreatic cancer expert at the University of Glasgow, said: “PRECISION Panc aims to transform how we treat pancreatic cancer by matching the right treatment to the right patient. Because the disease is so aggressive, patients may receive no treatment at all or if they are given an option it will be for just one line of treatment, so it’s essential that the most suitable treatment is identified quickly. It’s important we offer all patients the opportunity to be part of research alongside their standard care.”

The programme will ensure discoveries from the lab rapidly reach patients, and that data from clinical trials feed back into research of the disease. Cancer Research UK’s investment will support two of the three clinical trials, preclinical work, assay development, biomarker work and the huge amount of molecular sequencing. The charity’s funding will also provide overarching support though project management, funding staff, and a steering committee.

Professor Biankin added: “PRECISION Panc has been developed over the course of three years through the unwavering commitment of pancreatic clinicians and researchers who see that the patients deserve much more than is currently available to them. I’m fully committed to this project and I believe we’re on the cusp of making some incredible advances which will provide therapeutic options to help people affected by this terrible disease. Without Cancer Research UK and their vision for cancer precision medicine, and the commitment of the other stakeholders, we couldn’t get PRECISION Panc up and running.”

Dr Ian Walker, Cancer Research UK’s director of clinical research, said: “This ambitious project marks a new era for pancreatic cancer. Little progress has been made in outcomes for pancreatic cancer patients over the last 40 years, and we believe that PRECISION Panc will reshape how we approach treatment development. Cancer Research UK is determined to streamline research, to find the right clinical trial for all pancreatic cancer patients and to ensure laboratory discoveries have patient benefit.”

Image copyright Dr Eric O’Neill, CRUK / MRC Oxford Institute for Radiation Oncology

Radiotherapy risks are much higher for smokers

Smokers treated for breast cancer have much higher risks than non-smokers of developing lung cancer or heart attack as a result of radiotherapy – according to a new study funded by Cancer Research UK and published in the Journal of Clinical Oncology.

The study shows that for non-smokers the long-term  risk of death from lung cancer or heart attack – caused by radiation – is only  0.5 percent. But for smokers, this increases to around 5 percent.

These findings are based on a worldwide study by the Early Breast Cancer Trialists’ Collaborative Group of the lung and heart radiation doses and risks among 40,781 women with breast cancer in 75 randomised trials of radiotherapy.

Because modern breast cancer radiotherapy techniques have improved and are now better at sparing the lungs and heart than those used in the trials, the researchers also reviewed recent literature so they could take into account how radiotherapy is better targeted today.

Dr Carolyn Taylor, radiation oncologist and lead author from the University of Oxford, said: “For non-smokers, the absolute risk of death from the side effects of modern radiotherapy is only about 0.5 percent, which is much less than the benefit. But for smokers, the risk is about 5 percent, which is comparable with the benefit.

“Stopping smoking at the time of radiotherapy will avoid most of the lung cancer and heart disease risk from radiotherapy, and has many other benefits.“

Radiotherapy remains an important treatment for breast cancer and reduces the likelihood of dying from the disease. For most non-smokers or ex-smokers the benefits of radiotherapy will far outweigh any risks. But for some long-term continuing smokers, the risks may be greater than the benefits.

Dr Julie Sharp, Cancer Research UK’s head of health information, said: “This research highlights that breast cancer patients who smoke need to be offered help and support in order to try and quit to minimise any risks from their treatment. It’s important to remember that modern day radiotherapy techniques have been refined and improved to make sure it is targeted and effective while reducing the risk of side-effects.”

2017 Symposium Registration – Open now!

The day will be a celebration of the wealth of excellence we have here in Oxford, and the passion and commitment to cancer research that is shared across our community.

The 2017 symposium will focus on the themes of Prevent, Detect & Cure, and feature multidisciplinary speakers from across the University and Oxford University Hospitals NHS Foundation Trust.

Confirmed speakers include:

  • Prof Tim MaughanCRUK / MRC Oxford Institute for Radiation Oncology
  • Prof Xin Lu, Ludwig Cancer Research
  • Prof Zhengming Chen, Nuffield Department of Population Health
  • Prof Constantin Coussios & Prof Eleanor Stride, Institute of Biomedical Engineering

The event is exclusive for Cancer Research UK Oxford Centre members, and we look forward to welcoming you to the Saïd Business School on Friday 23rd June 2017.

Oxford Centre members can sign up here

CRUK Science Blog: Training viruses to be cancer killers

For decades, scientists and doctors have looked for ways to stop the damage that viruses cause to humans.

But in recent years, certain safe, modified viruses have emerged as potential allies to tackle cancer.

And our scientists are among those searching for new forms of cancer-killing viruses.

Previous studies have shown that some viruses naturally kill cancer cells, but how they do this has never been fully understood.

Professor Len Seymour’s lab, at the Cancer Research UK Oxford Centre, has been focusing on one particular cancer-killing virus that operates under the code name of Enadenotucirev (or EnAd for short).

And a new study, published in Molecular Therapy – Oncolytics, has revealed EnAd to have a rather unusual method of killing cancer cells.

Arthur Dyer, a researcher in Professor Seymour’s lab, and the team have installed their own version of ‘cell CCTV’ to catch the act of cell-killing on camera.

The footage below was recorded using a normal light cell microscope, commonly found in a lab that takes a snap every minute.

“Each frame is one photo taken every minute and then we’ve stuck all the photos together as a video,” says Dyer. The end result is the clip below:

Dyer explains: “Here we’ve got human lung cancer cells in a dish and we’ve infected them with a virus that’s trained to kill cancer cells.”

This lab technique has given researchers valuable intelligence as to how EnAd kills cancer cells.

“When the cells are infected with the virus they balloon up, blister and then die,” says Dyer, adding that it was a cause of cell death he’d never seen before.

“When I first saw it I thought I was going mad. It’s such a weird cell death, it seems to use up the energy in the cell which then causes it to swell.”

One of the ways in which viruses survive in the human body is by hijacking healthy cells’ internal machinery.

EnAd takes over the cancer cells’ machinery, using up the cell’s energy to such an extent that it has no more strength left to live.

“This virus needs cells that are already hyperactive,” adds Dyer, explaining that as the metabolism of cancer cells has gone haywire they make the perfect victim.

Cells normally die in a very controlled way, but these cancer cells balloon up to 2 or 3 times their size, giving the appearance of blistering.

And it’s this precise effect that gives EnAd potential to be a great cancer cell killer.

Cancer cells can disguise themselves from the body’s immune system, but when EnAd destroys cancer cells in the lab it leaves the ‘crime scene’ upturned, with lots of evidence carelessly left behind. Seymour’s team believe this could encourage the immune system to ring the alarm for other immune cells to come and investigate the scene.

And to test this further, they’ve been putting lots of versions of the virus to work in the lab.

Seymour’s team has made sure they’ve got the deadliest of cancer cell killers by using a tough training programme.

“Viruses are naturally good at killing cancer cells so even harmless ones have some ability to attack them,” says Dyer.

“But to find the best virus, we grow them repeatedly in cancer cells and compare them all head to head.”

It’s important that the virus can tell the difference between healthy tissue and cancer cells. So the team also tests them on healthy cells to make sure the viruses can’t grow in them.

“So at the same time we also look for the ones that are least able to infect normal cells,” says Dyer.

This tough selection process leaves the viruses with only one mission: to infect and destroy cancer cells.

EnAd has passed these lab examinations and is now being tested in an early stage clinical trial in a very small number of people.

“These trials are making sure the virus is safe and to find the best way to give it to the patient. Ideally we’d like to use an injection so the virus can get into the bloodstream and reach cells that have gone to other parts of the body,” says Dyer.

Some cancers can also become resistant to the ways in which treatments destroy them. But because EnAd has a different method of destroying cancer cells, Seymour’s team believes the virus might also be able to kill cancers that have become resistant to treatment.

Ultimately, the team hopes to test how it performs with other drugs and in specific types of cancer, bringing it that little bit closer to becoming a new ally for targeting cancer.

 

 

 

This blog post was originally published by Cancer Research UK. Author Gabi Beer.

Gold nanoparticles help deliver lethal one-two punch to cancer

Tagging gold nanoparticles with a small dose of radiation has helped researchers trace the precious metal as it delivers a drug right into the heart of cancer cells, according to new laboratory research being presented at the 2016 National Cancer Research Institute (NCRI) Cancer conference.

Researchers from the CRUK/MRC Oxford Institute for Radiation Oncology have been working on better ways to transport a drug directly into the control room of cancer cells, where the chromosomes are kept. This specific drug targets a molecule – telomerase – that builds up the protective caps at the end of chromosomes called telomeres.

In most cells of the body, telomeres act like an in-built timer to ensure that the cell does not live past its expiry date. Telomeres shorten each time the cell divides. Once a critical length is reached, the cell can no longer divide and it dies. Cancer cells manage to get around this safety check by reactivating telomerase allowing them to continue to grow out of control.

One of the biggest hurdles in treating cancer is getting effective drugs into cancer cells, particularly to where the chromosomes are stored. Gold nanoparticles have proven to be well suited to being absorbed into cells, safely delivering drugs that could otherwise be blocked.
By engineering the gold nanoparticles and adding the radioactive tracer, the researchers were able to prove that their drug was reaching the desired target in skin cancer cells grown in the lab and was shutting telomerase down, halting cancer’s growth.

While the radioactive tracer was used to precisely follow the drug in this study, the same method can also be used to deliver a dose of radioactivity to cancer cells, helping to kill them. This second dose is especially powerful because inactivation of telomerase makes cancer cells more sensitive to radiation.

Professor Kate Vallis, and Cancer Research UK Oxford Centre Member, said: “Gold is precious in more than one way. We have used tiny gold nanoparticles loaded with targeted drugs to kill cancer cells in the laboratory. Our long term goal is to design new treatments for cancer patients based on this promising approach.”

Sir Harpal Kumar, Cancer Research UK’s chief executive, said: “Gold has been used in medicine for many years and this research adds further insight into its potential. Ensuring that treatment is accurately targeted at cancer and avoids healthy cells is the goal for much of cancer research, and this is an exciting step towards that.”

Dr Karen Kennedy, Director of the NCRI, said: “Research continues to shed light on how cancer cells behave and how to effectively deliver a lethal payload to the tumour. This exciting research offers that potential and needs further investigation to see how it would be used in patients. The future looks exciting with research such as this improving the way the disease is treated.”

 

The Cancer Research UK Oxford Centre is at NCRI 2016, if you’d like to come and talk about the work of Oxford Centre members, come to stand 19 in the Exhibition Hall.

Photo of the 2016 NCRI Conference by Simon Callaghan Photography.