A new targeted treatment has been recommended by the National Institute of Health and Care Excellence (NICE) for some adults with advanced high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer
Niraparib will be available through the Cancer Drugs Fund as a maintenance treatment to enhance or prolong the effect of initial treatment. In this case, niraparib will be used after platinum-based chemotherapy for people with and without BRCA mutations.
Niraparib is a type of targeted cancer drug known as a PARP inhibitor.
Cancer Research UK researchers were involved in some of the earliest work into PARP inhibitors, which aim to kill cancer cells by stopping them repairing damaged DNA, in the early 1990’s.
PARP is a protein found in our cells that helps damaged cells to repair themselves. Cancer cells rely on PARP proteins to keep their DNA healthy to keep on growing and dividing.
As a cancer treatment, these inhibitors stop PARP from doing its repair work in cancer cells and the cell dies. PARP inhibitors were first trialled in combination with drugs that caused DNA damage – such as chemotherapy – to heighten the effects of these treatments. But researchers quickly realised the potential of these drugs to treat cancers that already had problems repairing cell damage, focusing on cancers with a change in genes known as BRCA.
Normally, BRCA1 and BRCA2 instruct cells to make proteins that help repair damaged DNA. Cells are less likely to repair themselves properly if they have a fault in one or both of these genes and people who have faulty BRCA genes have an increased risk of prostate, breast and ovarian cancer.
Cancer cells with BRCA gene faults already have a poor repair system. So blocking PARP with a PARP inhibitor drug in these cells causes DNA damage to accumulate, pushing cells over the edge.
Evidence from a large clinical trial shows that niraparib can give people who have already responded well to an initial round of platinum-based chemotherapy more time before their cancer gets significantly bigger.
During the clinical trial, people taking niraparib lived for an average of 13.8 months without their cancer getting bigger, compared to 8.2 months with a placebo.
Further analysis also indicated that niraparib increases the average amount of time before somebody’s cancer gets bigger for people whose cancer doesn’t have an error in either BRCA1 or BRCA2 genes, where there are currently no maintenance treatments available after initial treatment.
The PRIMA trial hasn’t been running for long enough to determine if niraparib can extend survival for people with high grade epithelial ovarian, fallopian tube or primary peritoneal cancers. The trial is still ongoing and further data could help to reduce uncertainties about the long-term impact of niraparib.
Clinical experts who helped make the decision explained that there is a high unmet need for more maintenance treatment options after first-line treatment for advanced cases of ovarian cancer.
“Evidence from clinical trials suggests that niraparib can delay the progression of someone’s cancer, potentially delaying the need for more chemotherapy and improving their quality of life. Because niraparib has been approved for use through the Cancer Drugs Fund, people will have access whilst more evidence on its longer-term benefits is gathered,” says Shrotri.
Uncertainties around the long-term benefits of treatment with niraparib meant it could not be recommended for routine use in the NHS at this time. However, its potential to be a cost-effective use of NHS resources meant niraparib could be approved via the Cancer Drugs Fund.
The Cancer Drugs Fund is a way for NHS England to give people access to new medicines while more data is collected on their long-term benefits.
NICE decisions are usually adopted in Wales and Northern Ireland, so this decision may benefit patients there too. Scotland has a separate process for reviewing drugs.Read more
Ever since the coronavirus pandemic brought the world to a standstill back in March, there’s been talk of a vaccine.
COVID-19 vaccines have been badged as our biggest opportunity to control the virus and return to normal. And for the last 10 months, researchers and scientists across the world have been racing to make that a reality.
With over 300 vaccines in development and 2 being rolled out across the UK, we wantto make sure everyone has access to information about the COVID-19 vaccine and what it could mean for people with cancer, so we’ll be updating this blog post as new data and information emerges.
From today, those aged 70, and over and those considered “clinically extremely vulnerable”, will begin receiving invitations for a COVID-19 vaccination. People considered “clinically extremely vulnerable” are those who were asked to shield at various points during the pandemic, and include:
The Department of Health and Social Care have acknowledged that those in the top 2 prioritisation groups – care home residents, those over 80 years old and front-line health care workers – will remain as the top priority to receive the vaccine.
The announcement today means that areas that have already vaccinated the majority of people in the top 2 priority groups will now be able to keep up the momentum and start vaccinating additional groups.
The UK Chemotherapy Board has produced a comprehensivedocument of FAQs onthe Pfizer–BioNTech and Oxford-AstraZeneca COVID-19 vaccines for healthcare professionals treatingpatientsonsystemic anti- cancer therapies (SACT) such as chemotherapy, antibody therapy or immunotherapy.
The document outlines that all patientsreceiving SACT should be considered foraCOVID-19 jab.
These FAQswere produced in response to questions by cancer specialists about giving the vaccine to people with cancer receivingSACT. They may be used bycancer specialists, along with any local guidelines, tohelp decide the best timing for giving the vaccines in people receiving SACT.
You can talk to your GP or cancer specialist when you’re offered the vaccine to discuss timings.We’ve got further information about the different vaccines, summarising the guidance from the UK Chemotherapy Board, here.
The Government has set out its latest vaccine delivery plan to administer at least 2 million vaccinations per week, as part of the ‘largest vaccination programme in British history’.
The plan includes the commitment set out last week by Boris Johnson to offer the first vaccine dose to all those in the top 4 priority groups, as recommended by the Joint Committee of Vaccination and Immunisation (JCVI), by 15 February. This includes those considered “clinically extremely vulnerable” including people with cancer who are undergoing chemotherapy, people with cancers of the blood or bone marrow, and people with lung cancer who are undergoing radical radiotherapy. You can find a complete definition of clinically vulnerable groups, on the Government website.
As part of plans to rapidly upscale the vaccination programme, the Government announced the goal to ensure that tens of millions of people will be immunised by the spring at over 2,700 vaccination sites across the UK.
The vaccine delivery plan also details the SIREN study – which will be used to continue to monitor vaccine effectiveness, including against the newer B.1.1.7 variant. The SIREN study is regularly testing healthcare workers for the virus and antibodies, and the recruitment will be expanded to ensure that people from areas where the new variant is spreading are included.
A vaccine made by Moderna –a US based biotech company –has become the third vaccine to be approved for mass rollout across the UK, although supplies are yet to arrive in the country and may not do so for several months.
This vaccine is the latest to have been approved bythe Medicines and Healthcare products Regulatory Agency (MHRA). Similarly to the Pfizer-BioNTech vaccine, which was approved in December 2020, the Moderna vaccine is not a ‘live’ vaccine, but contains a molecule called mRNA, which contains genetic information that causes the body to produce tiny fragments of a molecule made by the coronavirus.
In trials with more the 30,0000 people, the Moderna vaccine was assessed to see whether it could prevent symptomatic infection and was found to have an efficacy of almost 95%. There were also no cases of severe COVID-19 in the group that had the vaccine. It is unclear at this stage what impact the vaccine might have on infection without symptoms.
The Moderna vaccine can be stored at –20°C (normal freezer temperature) for up to 6 months.
The UK Government had originally ordered 7 million doses of the Moderna jab, but has since upped the order to 17 million to ensure that more people get vaccinated as quickly as possible.
This figure brings the total number of vaccine doses ordered by the Government to 367 million.
The news that 2 COVID-19 vaccines have been approved and are now being rolled out offers hope of a return to normal life in 2021. For people with cancer this could mean less anxiety about attending hospital appointments, fewer changes to treatment and shorter waiting times. At this stage, although we can’t be sure whether the vaccines will work quite as well in people having cancer treatment because of the effect that cancer treatment can have on the immune system, experience with other vaccines suggests that the COVID-19 vaccines should offer protection against COVID-19 for people with cancer.
Studies looking at how people with cancer have responded to the virus that causes COVID-19 may also provide some clues. Results just published from one of these studies – the SOAP study – suggest that patients with solid cancers have a similar immune response to the virus as people without cancer. Those with blood cancers were found to have a more variable response, with some people responding similarly to people with solid cancers, while others didn’t manage to clear the virus or develop antibodies against it. The numbers in this study weren’t big enough to determine whether patients with particular blood cancers or receiving particular treatments had a poorer response.
These findings may have implications for COVID-19 vaccination, for example it may be that some people with cancer would benefit from more frequent boosters or monitoring to check their response. The SOAP study plans to investigate this in the next phase of their project, which will look at the immune response to the vaccine in people with different type of cancer.
It’s important to remember that some protection is better than none and that people with cancer are encouraged to take the vaccine when it is offered. As with other vaccines, the timing of COVID-19 vaccination may depend on the type and timing of cancer treatment.
Are these vaccines safe? And which vaccines are most appropriate for people living with cancer? These are questions we’re frequently being asked, and understandably so.
While we’re not able to comment on individual circumstances, we’ll continue to update this blog post as new findings and information are released.
To get an ‘on the ground’ view, we recently spoke to Dr Neil Smith, a GP based in Lancashire, about how he is advising his cancer patients in his clinic. “My general advice is yes, it is, safe. You’ve got to understand your individual circumstance, but for people with cancer, or for people who have previously had treatment for it, it is safe. For most people, it’s much safer to have it than not have it. And because it’s not a vaccine that uses a ‘live’ virus, it doesn’t pose a threat to somebody’s immunity, instead It helps them to produce their own immunity against the coronavirus.”
The Medicines and Healthcare products Regulatory Agency (MHRA) – the organisation which grants licenses to companies to sell their medicines in the UK – have confirmed that both the Pfizer-BioNTech vaccine, and the Oxford-AstraZeneca vaccine, are safe for rollout across the country. Whilst doses of the other vaccines have been purchased, they are yet to be approved by the MHRA.
Similarly, another government body – the Joint Committee on Vaccination and Immunisation (JCVI), which advises UK health departments on immunisation – commented that the Pfizer-BioNTech vaccine “appears to be safe and well-tolerated, and there were no clinically concerning safety observations,” and that the Oxford-AstraZeneca vaccine “appears to have a good safety profile.” These comments apply to the general population – but what about people affected by cancer?
Some people who were asked to shield during the pandemic (and who are considered “clinically extremely vulnerable”), which includes a number of cancer patients (please see the update from 28 November for the complete list), will be prioritised to receive their first dose of vaccine as soon as possible. However, the JCVI thinks that others who are considered “clinically extremely vulnerable” and who also have some degree of immunosuppression, or are immunocompromised, may not respond as strongly to the vaccine – despite this, the vaccines will, they think, still offer these people some protection. So the COVID-19 vaccines are likely to be made available to cancer patients at some point. However, these people, including those on chemotherapy, have been advised to continue to follow Government shielding advice to reduce their risk of infection, even after vaccination.
Whatever their situation, people invited for vaccination will be able to discuss their concerns with a doctor. “When people arrive at a COVID-19 vaccine centre, they’ll go through a normal consent process. And within that consent process, if there’s any specific issues, they’re often advised beforehand to contact the GP, and so a GP will be in contact with several patients wanting a bit more information,” says Smith. “But in my experience of that, it’s been a very positive conversation where I’ve been able to reassure people – ‘Yes, the vaccine for you is safe, and you should go ahead’.”
Smith is extremely hopeful for the vaccine. “It’s one of the best things I’ve seen in my 30 years of the NHS, and the main thing it does, is it makes the world a better place and makes us safer. So what I’m hoping going forwards, it’s safer for me to see patients and it’s safer for patients to feel confident they can see me to talk about cancer again, and to talk about the fears and concerns, it’s safe for me to refer them and to do investigations, and it becomes much safer for people to carry on having the cancer treatments early. The COVID-19 vaccine will help us to continue to diagnose and cure cancer and save people’s lives.”
The Oxford-AstraZeneca vaccine has been approved for use in the UK. It is the second jab to be approved in the UK after the Pfizer-BioNTech vaccine was given the go-ahead earlier this month.
This vaccine contains a weakened form of a common cold virus (harmless to humans) that has been modified to include the gene for the coronavirus spike protein. Once injected, this primes the immune system to attack without exposure to the full virus. This is then followed by a second dose – up to three months later – for maximum protection.
The Government has ordered 100 million doses – enough for 50 million people – with the first due to be given out on 4th January 2021. According to a spokesperson from the Department of Health and Social Care, “the priority should be to give as many people in at-risk groups their first dose, rather than providing the required two doses in as short a time as possible.”
Speciality vaccine company Valneva is the latest to begin clinical trials of their COVID-19 vaccine, currently being developed in West Lothian in Scotland.
The Valneva trial will begin by testing the safety and efficacy of the vaccine on volunteers at 4 sites across the UK and is currently enrolling 150 healthy participants aged 18 to 55.
The Valneva vaccine is what’sknown as an “inactivated whole virus” vaccine. While the vaccine does hold some of the same virus particles that cause COVID-19, they are weakened and made inactive so that they cannot give you the virus. But they are able to prime the immune system to be able to recognise and destroy the virus responsible for COVID-19, which may prevent you from getting sick if you’re exposed to the virus in the future.
If these initial phase trials are successful, further trials, on larger groups of volunteers, have been planned for next year.
The UK Government has already pre-orderedthe vaccine developed by Valneva, and if the clinical trials are successful in proving the vaccine is safe and effective, 60 million doses could be made available by the end of 2021.
To date, the UK has secured early access to 357 million doses of 7 of the most promising vaccine candidates, including:
Results from the clinical trial ofthevaccinedeveloped byPfizer/BioNTech – currently being rolled out across the country –have been published inThe New England Journal of Medicine, showing that the vaccine may provide protection as early as 12 days after the first dose.
The phase 3 trial involved 42,000people, with around half receiving the vaccine and the others a dummy vaccine (placebo). 170 peopledeveloped COVID-19, with 8 cases in the vaccinated group and 162 in the placebo group,demonstrating that the vaccine has an overall efficacy of 95%.
Efficacy looks at whether an intervention (e.g. a drug or a vaccine) works under optimal conditions (such as a clinical trial). As an example, some of the COVID-19 vaccines are being tested in healthy participants or in people who are at higher risk of catching the virus because of their job, rather than being tested in the whole population.
Effectiveness looks at whether an intervention works in the ‘real world’.Vaccineswill continue to be monitored after they’ve been rolled out. The data collected helps experts understandhow well they work in different groups of people (looking at factors such as age, ethnicity, people with health conditions, etc) and how long the protection given by the vaccine lasts.
The AstraZeneca Oxford vaccine have also been published, this time in The Lancet, with data suggesting that the vaccine is safe and offers protection against COVID-19.The results are a combination of 2 clinical trials in the UK and Brazil. When the interim trial results were released a few weeks ago, the vaccinehad an efficacy between 62 and 90% depending on how doses were administered.
This paper shows that the vaccine offers protection againstsymptomatic COVID-19when the2 doses are administered with a 6-week gap between them. This could mean that this vaccine could take longer to roll out than others, with the Pfizer vaccine being given in2 doses spaced as little as3 weeksapart. However, it doesn’t need to be stored at –70 degrees, meaning that it might be easier (and perhaps cheaper) to deliver.
The development of multiple COVID-19 vaccines over an extraordinary 10-month period has brought up some questions about why there haven’t been similar transformative leaps in treating cancer.
Cancer is a highly complex disease, with over 200 different types that vary in biology, genetic make-up and behaviour. Not only that, but each person’s cancer is unique with its own set of challenges, so it’s very unlikely there will ever be one single cure that can be applied to everyone.
One of the biggest challenges our researchers face is that cancer can evolve, adapt and diversify and eventually outwit the immune system. For now, COIVD-19 doesn’t appear to rapidly change its make-up like cancer. And with COVID-19, researchers have been able to define specific targets that are found on the virus, which makes it much easier to treat than cancer.
Much of the science behind the development of the recent COVID-19 vaccines have been underpinned by previous research to understand the body’s immune system for other diseases, including cancer. And the extraordinary progress of the COVID-19 vaccine is in part because scientists, governments, industry and academic institutes around the world turned their focus to this one goal. To further accelerate development, different phases of vaccine trials and production have overlapped.
Although progress against cancer might not look as quick or dramatic as that against COVID-19, we have made great strides. Thanks to our research, we’ve helped cancer survival double over the last 40 years.
But there’s still more to do, and the technologies and insights that have come from the COVID-19 vaccine work could help us with future advancements in cancer research. We are relentless in our ambition to beat cancer and will continue to fund ground-breaking research to find new ways to prevent, diagnose and treat cancer.
90-year-old Margaret Keenan has become the first person to receive the Pfizer-BioNTech COVID-19 vaccine, as mass rollout begins across the UK. BBC News has the latest.
50 hospitals in England have been selected to receive the first doses of the vaccine and deliver the first rounds of the vaccination programme. Scotland, Wales, and Northern Ireland are also set to begin their vaccination programmes from hospitals today.
With the first 800,000 doses arriving this week, limited quantities will be available until further doses arrive. To begin, elderly people who are hospital outpatients, as well as those who are being discharged after a stay in hospital, will be among the first to be offered the vaccine. Each individual will require two jabs, administered within 21 days of each other, so the initial 800,000 doses will vaccinate 400,000 people.
Prioritisation groups are based on who has the greatest risk of becoming seriously ill or dying from the virus.
The UK has become the first country to approve the Pfizer–BioNTech vaccine for widespread use, after the Medicines and Healthcare products Regulatory Agency (MHRA) confirmed that the vaccine is safe for rollout across the country.
The mRNA vaccine, which trials suggest offers up to 95% protection against COVID-19, should be available to those who need it most, including elderly and care home patients and staff, within the week. Protection from the vaccine should stop people from becoming ill with the virus. So far, the UK has ordered 40 million doses, enough to vaccinate 20 million people, with the first 800,000 doses arriving early next week.
The vaccine will be distributed from Pfizer centres in Germany, Belgium and the USA. Approximately 50 hospitals across the country have been prepared to deliver the first of the vaccination programme. Specialist vaccination units in spaces such as conference centres are also being set up and some GPs and pharmacists may have access to vaccines, if they have the available cold storage facilities required to store the jab.
To find out more, head to BBC News.
The final results from Moderna’s vaccine trials have confirmed that their vaccine showed 94% efficacy against COVID-19, and nobody who received the vaccination developed a severe case of the virus. The latest news has initiated an approval process with regulators around the world who will study the trial data for the vaccine and decide if the data on its safety and effectiveness are robust enough to be recommend for roll out.
The UK has now bought 7 million doses of the vaccine, which are expected to arrive in the UK in March. On top of that, the UK has pre-ordered 40 million of the Pfizer/BioNTech vaccine and 100 million of the AstraZeneca Oxford vaccine. Full trial data has not yet been released but you can read more about the Moderna vaccine at BBC News and The Guardian.
The provisional priority list published by Public Health England has listed people aged 18 years and over who are deemed “clinically extremely vulnerable” as the same priority as the over-70s to receive a COVID-19 vaccine.
People considered “clinically extremely vulnerable” are those who were asked to shield during the pandemic, and include:
Although this prioritisation list is subject to further potential changes as the vaccine is still waiting approval from the Medicines and Healthcare products Regulatory Agency (MHRA), those considered “clinically extremely vulnerable” have now been placed in priority group 4 of 9. Based on these changes, the interim guidance, advised by the Joint Committee on Vaccination and Immunisation (JCVI), says the order of priority should be:
The day’s big news was of results from clinical trials in Britain and Brazil of the vaccine led by drug company AstraZeneca and researchers in Oxford. The trials involved over 20,000 individuals and showed differing levels of protectivity depending on how the doses were administered (between 62 and 90%). Like all the recent results, these findings were announced in a press release and have not yet been independently verified.
There are more than 300 vaccines in developments, many in the final stages of testing. The vaccines are all aiming to protect people against developing COVID-19, but they’re produced in different ways.
The main vaccines that have reported results so far are:
The trials explicitly excluded people with a history of cancer apart from a few exceptions; those with localised prostate cancer (where the cancer is contained in the prostate and has not spread to anywhere else), non-melanoma skin cancer that has been treated, cervical carcinoma in situ (pre-cancer) that has been treated, or those with a low risk of either their cancer coming back, or spreading to other parts of the body.
So far, we haven’t seen any data about how effective the vaccine was in these people, nor how many were on the trials – we’ll be looking out for this information as it emerges.
The UK government has already pre-ordered 100 million doses of this vaccine.
In addition to vaccine development, AstraZeneca have started large-scale trials of an “antibody cocktail” aimed at providing short-term protection to people with a weakened immune system, who would be unlikely to develop immunity after a vaccine. Antibodies form a key part of the immune system’s response to infection and it’s hoped that these antibodies developed in the lab will help the immune system to fight off the virus. AstraZeneca have described it as “almost like a passive vaccination.”
5,000 people around the world will be taking part in the trial of this treatment that scientists hope could give individuals immediate protection lasting up to 1 year. If successful, this may make up part of the UK’s wider COVID-19 treatment portfolio and be available to people whose immune systems are compromised.
Like most of us, Cancer Research UK-funded experts have been following the news closely and have called the progress‘exceptional’.
News of an effective COVID vaccine is great to hear. Having a vaccine will make the world safer, which means it will be safer for people with cancer too and it will become much easier for cancer treatments to continue.
We look forward to getting a better understanding of the best time to give the vaccine to cancer patients to give them the best level of protection.
– Martin Ledwick, Cancer Research UK’s head information nurse
Normal drug or vaccine development would take in the range of 5-10 years, sometimes much longer, so these developments have been extraordinary.
But experts have been keen to emphasise that the rapid turnaround of the COVID-19 vaccines isn’t because standards have dropped. In fact, the COVID-19 trials have involved more people than standard vaccine trials and have been able to draw on cutting-edge developments in technology and data analysis.
The extraordinary progress is in part because scientists, governments, industry and academic institutes around the world have turned their focus to this one goal. And to further accelerate development, different phases of vaccine trials and production have overlapped.
Finally, while the initial results are extremely promising, it’s early days yet. Preliminary data from one vaccine trial led by Pfizer suggested the vaccine offered 90% protection against developing COVID-19, whilst more recent data revealed the vaccine was 94% effective in over-65s. Initial reports from a second vaccine trial made by Moderna disclosed similar figures.
Experts expect more results – including important safety data – to materialise in the next 4 to 6 weeks. Vaccination will only be approved once it has passed the usual high standards set by the Medical and Healthcare products Regulatory Agency (MHRA) in the UK.
You can read more about the various COVID-19 vaccines in this piece by journalist Tom Chivers, who’s taking part in the Oxford-AstraZeneca vaccine trial.
We don’t have information on how many people living with cancer, or with a history of cancer, have been involved in COVID-19 vaccine trials so far. But some people with cancer have been able to take part in these trials, although who can take part varies from trial to trial.
For example, the earliest phase of the Pfizer trial involved healthy people aged 18 to 55 or 65 to 85. People with pre-existing conditions were able to take part as long as they didn’t require a significant change in therapy or hospitalisation for worsening disease in the 6 weeks prior to enrolment.
In later phases of the trial (phases 2 and 3) the lower age limit was reduced to 16 years old and individuals identified as being in a ‘high-risk’ group based on their use of public transport, being a frontline essential worker or other factors were included. Although people with cancer weren’t explicitly excluded from this list, those who are immunocompromised or receiving immunosuppressive therapy were not able to take part, and anyone taking part needed to have stable disease prior to enrolment.
For the late phase trials of the Oxford vaccine, anyone over the age of 18 who’s considered to be ‘medically stable’ – someone who’s not expected to be hospitalised or change their therapy less than 3 months before enrolment – could enrol in the trial. The criteria for the Oxford trial explicitly excludes anyone with a history of cancer, apart from a few cancer types, or those with a low risk of either their cancer coming back following curative treatment or spreading to other parts of the body.
Another vaccine that’s hit the news recently is the Moderna vaccine. Similar to the Oxford vaccine trial, medically stable people aged 18 or over were able to take part in the Moderna vaccine trials. However, those who are immunocompromised or have taken immunosuppressive treatments in the 6 months before the trial were not able to enrol.
Beyond vaccine trials, studies looking at how people with cancer’s immune systems respond to COVID-19 may also provide useful information on if the vaccine will be effective for people with specific types of cancer.
Lilly, Katie, Angs and LyndsyRead more
25 years ago, a team of our scientists were celebrating. Their risky strategy had paid off.
“You look back and you do wonder about how we decided to do this, and basically it was because we believed that it was better to do high-risk research that potentially would be important,” recalls team leader Professor Mike Stratton, “but with the full knowledge that, perhaps, the gene didn’t exist.”
But exist it did – in fact, the team had just pinpointed the location of what would become one of the most famous ‘cancer genes’ known to science – BRCA2.
And in the process, they opened the door to ways to give people more certainty about their risk of cancer and paved the way for new and better treatments.
The hunt for ‘breast cancer’ genes began in the 1940s, when researchers discovered that the disease could occasionally run in families. It became clear in the following years that these clusters of breast cancers in families were caused by faulty genes.
But pinpointing the specific genes responsible would take decades. We’ve written before about the race to discover the first breast cancer gene, dubbed Breast Cancer 1 or BRCA1, which was found to sit on chromosome 17 in 1990 by a team of US researchers.
“Much of the focus after BRCA1 was located was on clarifying that discovery, confirming it and narrowing down exactly where BRCA1 was,” says Professor Stratton, who is now the Director of the Wellcome Sanger Institute in Cambridge, UK. “But we decided to do something different.”
There was evidence that BRCA1 might not be the only gene linked to breast cancer. Could there be another? Stratton, who back then had only recently started leading his own group at The Institute of Cancer Research (ICR), turned his focus to the hunt for a second gene. It was a risky strategy.
“Whether there was one or not, was not at all clear at that time. Indeed, there were those who felt strongly that there was only one of these high-risk genes and that BRCA1 was it. Nevertheless, we felt that if there was a second gene like it, that would be an important thing to follow through.”
With funding from one of our forerunners – Cancer Research Campaign – the Medical Research Council and others, Stratton’s team began searching. The first thing they needed was a collection of families who were strongly affected by breast cancer, which led them to Ireland.
“We wrote to all the oncologists and one replied, Peter Daly. He was working with a family in Ireland who had 4 cases of breast cancer, 4 sisters who were diagnosed at a young age. By the time we started working with him that had become 5 sisters. And our first job was to find out whether this cluster was due to BRCA1.”
Early on, the team got a signal that it wasn’t, which gave them strong evidence that another gene existed.
Armed with this knowledge, the team followed a similar process that led to the localisation of BRCA1, scouring the human genome for stretches of DNA that everyone in the family who had breast cancer had in common. But after 7 months, they hit a wall. “We really couldn’t find it. It was one of those moments when your team looks to you for inspiration or new ideas, and the best I could come up with was: let’s do it all again. So we did.”
The team’s persistence paid off. Stratton says he remembers the afternoon that one of his team, Richard Wooster, came into the office with an x-ray film that appeared to show the location of the elusive second gene, on one of the 23 different chromosomes that makes up the human genome. “We came into work that morning not knowing where the gene was, and we went home that evening knowing it was on chromosome 13.”
The next step was to precisely identify which gene on this massive stretch of DNA was responsible – something that, back before the publication of the full map of the human genome, was a painstaking task. And it quickly became a race, as former collaborators in the US teamed up with a genetics company who wanted to find and patent the gene, something that Stratton was strongly against.
Teaming up with labs across the world, including that of his colleague Professor Alan Ashworth at the ICR and scientists at the Wellcome Sanger Institute, they began the laborious process of identifying which gene on chromosome 13 was BRCA2.
“It seems amazing looking back that we had to physically find genes, rather than just looking them up,” says Ashworth. “But the human genome wasn’t available at that time.”
After homing in on a section of DNA with abnormalities, the team worked tirelessly unscramble the mess and check if similar faults were also found in other samples in the same region. It was painstaking work, but it paid off. They had found BRCA2.
“It was a real rollercoaster, the intensity of work by the team that went into that final phase was absolutely extraordinary,” says Stratton. “And it was an amazing collaboration with other groups and the support of so many families who had been affected by breast cancer.”
The team published their findings in the journal Nature in December 1995, 25 years ago.
The discovery had an almost immediate impact. “We had a lady whose family had many cases of breast cancer. We didn’t know at the time whether those cancers were caused by BRCA mutations, but what we did know through working with her was that she did not want to get breast cancer.” With a young family to keep in mind, the woman was considering having preventative surgery to remove her breasts.
“But when we discovered BRCA2, it was possible to sequence her DNA and the DNA of members of her family to identify what was responsible. It turned out that other family members carried BRCA2 mutations, but she didn’t. So she was saved from having that surgery.”
Carrying a fault version of a BRCA gene means a woman has around a 70% chance of developing breast cancer by the age of 80, compared with around a 12% chance in the general population – though this does vary with other breast cancer risk factors.
BRCA2 mutations are also linked to prostate cancer, with one cohort study showing that prostate cancer risk is up to 5 times higher in men with BRCA2 mutation compared with the general population.
Since then, Stratton estimates that hundreds of thousands, if not millions, of people have been tested for BRCA1 and BRCA2 faults, giving them more certainty about their future, as well as options to reduce their risk, including surgery or preventative drugs.
The discovery of BRCA genes also paved the way for research that’s identified more subtle DNA variations that could impact someone’s risk of cancer. This knowledge is now being tested in the clinic, with our scientists creating the most comprehensive method yet to predict a woman’s risk of breast cancer in 2019, taking into account more than 300 genetic indicators.
But the story doesn’t stop there. Following the discovery of BRCA2, Ashworth and others worked to understand what it actually did and how it was linked to cancer. “We uncovered a particular function of BRCA2 in a DNA repair pathway,” says Ashworth. This kicked in when both strands of the DNA double-helix ‘ladder’ are broken – a situation that can be catastrophic for a cell. “And that gave us an insight into how to treat BRCA-mutated cancers.”
Both BRCA1 and BRCA2 instruct cells to make proteins that help repair damage to their DNA – something that occurs constantly over a cell’s life. But if a cell picks up damage to either BRCA gene, then its ability to repair its DNA is impaired, increasing the chances of the cell becoming cancerous.
But there’s a catch. As cells can only tolerate so much damage before they die, BRCA faults also push them closer to the edge – a discovery that Ashworth was keen to exploit.
With BRCA-mutant cells’ DNA repair systems already impaired, Ashworth’s team believed that impairing it further might tip cells over the cell, killing them. And they were right. In 2005, scientists showed that cancer cells bearing BRCA faults were exquisitely vulnerable to experimental cancer drugs known as PARP inhibitors, which are designed to hobble a completely separate part of a cell’s DNA repair system.
It’s a discovery that oncologist Professor Ruth Plummer remembers well. Plummer was already the first person in the world to have written a prescription for a PARP inhibitor, with the first PARP inhibitor developed by the Newcastle Drug Discovery team and funded by Cancer Research UK. This drug, now licensed as rucaparib, was already in trials in combination with chemotherapy. But the potential of PARP inhibitors in BRCA cancers excited Plummer further.
“I saw the data from the Newcastle group before it was published and within 6 weeks we’d applied to Cancer Research UK to do the first ever BRCA-focused clinical trial with a PARP inhibitor.
“It was really exciting because although at that point we still hadn’t got the dosing right, or worked everything out, the second patient we ever trialled this on responded. So we got a signal really early on that the scientists could be right.”
There are a now a number of PARP inhibitors – including olaparib and rucaparib – licensed for people with BRCA-related ovarian, breast, fallopian tube, pancreatic and prostate cancers. Over 30,000 patients have been treated with olaparib so far and that number is growing rapidly.
It’s also becoming increasingly clear that PARP inhibitors like olaparib and rucaparib are effective in treating a wider group of patients with DNA repair defects, with trials ongoing. And researchers aren’t stopping there. As well as developing new and better ways to predict who could respond to PARP inhibitors, Plummer is also involved in trials testing whether combining a PARP inhibitor with immunotherapy treatments is beneficial.
“The discovery of BRCA2 has had a huge impact on my life, and that of my children and my family. Finding out that I had the gene was obviously hard to process, and it was difficult to think about the future of my family, but it is so much better to have this knowledge.”
Mum-of-two Natalie Hall, 45, from Marlow, was diagnosed with breast cancer in 2019. She did not discover until months after diagnosis that there had been cancer on her father’s side too. She subsequently tested positive for the BRCA2 gene.
“For me, it meant that I had a preventative double mastectomy and an oopherectomy after my original breast cancer treatment.” The discovery that Natalie had a BRCA2 fault also meant that her cancer could be targeted with an extra chemotherapy that was thought to be more effective.
“The knowledge about BRCA2 has potentially given me my life and more options for my children too. I would like to thank the scientists for their work, and to highlight all the research that has happened as a result of that discovery to improve treatments.”
25 years on, it’s a completely different world for scientists like Ashworth and Stratton, both in terms of the information that’s available to us and the technology to exploit it, largely due to the work of the Human Genome Project.
It’s strange to look back for Ashworth. “On one hand, it feels like yesterday, on the other hand, it feels like a different age.” And while the scientists didn’t get to celebrate the occasion in person, the work will always mean a lot to those who were there. “To this day, when I meet someone who has been treated with a PARP inhibitor, it gives me a shiver to think I played a part in its development.”
But while the technology has moved on dramatically, Stratton’s approach to research remains unchanged. “Asking those big, high-risk questions brings many joys and potentially much success. You’re continually aware that you might fail in the race, or the thing you’re chasing after might not exist, but if it does the impact will be huge. So, that’s always the way we have operated.”
This week, NHS England began to inform people that one of the bowel screening tests – bowel scope – will no longer be a part of the bowel screening programme in England.
The test, which uses a thin, flexible tube with a small camera and light at the end of it to look inside the lower part of the bowel, aims to find early-stage cancers that aren’t yet causing any symptoms. And in a trial we part funded, the test prevented more than half of the potential bowel cancers from developing in the bowel and reduced the risk of dying from these cancers by two thirds in people who were screened.
Based on the evidence, bowel scope implementation began in England in 2013, with a plan to offer it as a one-off test to men and women aged 55 years. The test was never introduced in Scotland, Wales or Northern Ireland.
At the time, NHS England said the roll out wouldn’t be immediate – it was estimated that it would take at least 3 years before the test would be offered to everyone eligible because of a shortage of trained staff – endoscopists – to carry out the test.
But 7 years after roll out began in England, bowel scope was still not being offered to everyone. And it’s now been removed from the roster altogether.
Roll out of bowel scope had a number of challenges, with one of the biggest being the availability of staff to do the bowel scope test. Health Education England developed a clinical endoscopist programme to help train more staff to do bowel scope, but unfortunately this was still not enough to meet the full workforce need.
More recently, endoscopy services have been put under even more pressure by the introduction of a new test into the bowel screening programme – FIT (Faecal Immunochemical Test) – and services looked at ways to manage the demand. Some centres decided then not to do bowel scopes.
And then COVID-19 hit. The pandemic caused further disruption to the delivery of endoscopy services for both screening and symptomatic referrals. Bowel scope was often at the bottom of the list when it came to getting services back up and running and working through the significant backlog of patients that had built up.
With all that in mind, NHS Englandconsulted with a range of organisations and experts, including the National Screening Committee (NSC) and recommended thatbowel scope should be officially stopped in England. TheSecretary of State has sincesupported this decision, so that attention could be focused on extending the age range for FIT bowel screening.
It’s disappointing that bowel scope screening is being formally stopped now, but we understand why this decision has been made. Ongoing staff shortages have meant that bowel scope never reached its full potential and the pressure of COVID-19 on the health system was the final straw.
– Dr Jodie Moffat, Cancer Research UK’s head of early diagnosis
The decision and the disruption of the past couple of years mean there are thousands of people who have accepted an offer of a bowel scope but have not had the test. And now that the decision has been made to formally stop bowel scope, they will not receive one. Instead, this particular group of people will be directly contacted by the NHS from mid-December, and will be offered a FIT, though our understanding is that this will not be sent out until Spring 2021.
Later, when this group of people falls within the eligible age range for bowel screening (60-74 year olds), they will be offered the FIT every 2 years, as will people who have either never been invited for bowel scope, or were invited but didn’t take up the offer.
While the loss of bowel scope is discouraging, there are positive changes to the bowel screening programme on the horizon.
NHS England has committed in line with National Screening Committee recommendations to extend the age range of FIT bowel cancer screening, so that anyone aged 50 years and above will ultimately be invited to take part in the bowel screening programme.
Bowel cancer screening, where a home testing kit is sent out, is currently offered to everyone between the age of 60 and 74 in England, Wales and Northern Ireland, and between 50 and 74 in Scotland. It aims to detect bowel cancer at an early stage when treatment is more likely to be successful.
It’s your choice to take part in cancer screening or not, but we would encourage people to consider taking part in the bowel cancer screening programme.
It’s important to remember screening is for people without symptoms. Whatever your screening history, if you notice any unusual or something that doesn’t go away such as blood in your poo or a change in bowel habit, tell your doctor.
And there are further changes that could be made to improve the at home bowel screening test. There is potential to increase the sensitivity of the FIT, to help pick up more cancers and more adenomas that could potentially develop into bowel cancer as we’ve written about before. We want to see all UK nations reducing their thresholds to that recommended by the UK’s National Screening Committee.
But importantly, we must learn the lessons of bowel scope. NHS England now needs to publish a timeline for when both of these changes will be comprehensively implemented, guarding against the geographical variation we had seen with bowel scope. To achieve this will require investment from the Government in endoscopy and pathology services.
In the recent Spending Review, the Government invested in training more staff in the next year, but we need to see a multi-year commitment to increasing the diagnostic workforce and kit if we are to improve bowel cancer outcomes in England and achieve the ambitions in the NHS Long Term Plan, as we’ve written about before.
Moffat says it’s vital that staff shortages do not continue to dictate what services the NHS is able to provide.
“The current FIT bowel screening programme will save lives from bowel cancer, but the NHS needs more staff and equipment to clear the backlog and to ensure that the improvement plans, which will mean more people are invited for FIT bowel screening, can be rolled out quickly and fairly across the country.”
Rachael Ogley is an early diagnosis manager at Cancer Research UKRead more
Philanthropy and partnerships
Since 2017, Co-op Legal Services and Funeralcare have supported our work by raising funds from sales of their special packages, including wills and lasting power of attorney – as well as through the generous donations of their customers. They’ve also helped generate a significant sum in pledged donations as one of the providers for our Free Will Service. As they celebrate reaching £200,000 raised for life-saving cancer research, Head of Corporate Partnerships, Jonathan Appleby, and Head of Wills, James Antoniou, tell us what our partnership means to them.
JONATHAN: The Co-operative Group has a long history of taking the lead on the issues that matter most to our members, from being one of the first businesses to recognise the need to tackle climate change, to our many ‘Fairtrade firsts’ and our campaigns for social justice. Its values and principles are as relevant today as they were when we were founded in 1844, and they remain at the heart of our thinking about the challenges facing society today. Our vision, ‘co-operating for a fairer world’, supports our planning for a successful and sustainable Co-op that maximises the value we generate for members, communities and other stakeholders.
JONATHAN: We’re proud to work with an amazing charity that works hard to fight cancer and support those affected by it. At Co-op Legal Services, we look to ensure clear synergies between our partners and the values and ethics of our own operation. Clearly, with Cancer Research UK there is this parity. Our mission is to make legal services accessible to more people and by partnering with the charity, we’re able to deliver this while helping to fund further research into cancer.
JONATHAN: For me, there are many factors. First, there need to be shared objectives that meet a genuine customer need and, in the case of Cancer Research UK, support a cause that is close to our customers’ hearts. Second, it’s vital to establish clear lines of communication between organisations. Third, partnerships need to evolve. It’s important to always seek ways for a partnership to grow and adapt to the changing environment to ensure that it remains relevant. We’re thrilled to have reached the £200,000 milestone thanks to the support of our customers and colleagues. And there are many opportunities for our partnership to evolve – we look forward to continuing this journey.
Finally, and this is particularly important with legal services, the partnership must always act in the best interests of the customer. Any partnership recommending a legal service to a potential client must be transparent in terms of what it is and how it delivers on the client’s need. For wills, this means providing suitable advice on the best will for the customer and ensuring that the detail and protection are checked.
JAMES: I think a combination of factors are involved. Clearly, the high infection and death rates reported in the media have accelerated people’s decisions to get their affairs in order and make a will. I also believe the national lockdowns and the Government’s furlough scheme have given people more time than ever to consider their own wishes and to put their wills in place. More and more people are recognising the importance of making a will as the only way to choose how you want your money and assets to be distributed following your death. Without a valid will in place, the law will make this decision for you based on the value of your estate and the categories of relatives that are still alive after you’ve died.
JAMES: I imagine every single person in the country has lost a loved one to cancer or knows of someone who has received treatment. Cancer impacts all of us and my hope is that, collectively, we can contribute and raise funds for research to help improve survival and ultimately find cures. I’m very proud of our partnership with Cancer Research UK because I know that the contribution that Co-op Legal Services has made and continues to make is helping to give us all a better chance of beating cancer.
Edward Bowers is a senior partnership relations executive at Cancer Research UKRead more
Data di pubblicazione: 19/01/2021Read more...
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