THE CANCER TREATMENT BREAKTHROUGHS PUSHING US CLOSER TO A CURE
Cancer survival has doubled in the past half a century, but around 167,000 people still die of the disease in the UK every year. Much of this is down to ever-growing waiting lists – health officials are now considering ways for patients to skip the GP stage and go straight to see specialists.
In recent years, there have been many exciting steps forward in medical science. Kevin Harrington, a professor of biological cancer therapies at The Institute of Cancer Research and an honorary consultant oncologist at the Royal Marsden (RMH) and St George’s Hospital in London, is optimistic that advances in treatment will improve outcomes.
“In 20 years, I confidently expect we will cure a substantially larger number of cancer patients,” he says. “And we will cure them with far smarter and kinder treatments than current approaches.”
This does not mean there will ever be a single cure for cancer, says Dr Claire Bromley, a senior science communications manager at Cancer Research UK.
“Cancer is not a single disease”, she adds. “There are over 200 types of cancer, and all of them can be split into different subtypes. It’s unlikely that there will be one silver bullet. However, a combination of many different treatments means we can ultimately beat cancer for everyone.”
Here are the newest breakthroughs to celebrate:
The take-at-home tablet that ‘disarms’ cancer
What is it?
The drug, known as KCL-HO-1i, is a tablet that works by disarming a defence mechanism that tumours use to protect themselves. Early tests on mice found the drug even helped chemotherapy-resistant tumours to respond to treatment.
It is hoped KCL-HO-1i can be trialled on humans, with researchers suggesting it could one day be a “valuable companion drug” to chemotherapy, helping patients to avoid more aggressive treatments.
Chemotherapy is used to treat many kinds of cancer and works by disrupting the way cancer cells grow and divide. However, it is not as effective as it should be in some patients because the body’s own immune cells can act as a barrier around tumours. These cells produce a protein called heme oxygenase-1 (HO-1), which helps shield the tumour from the immune system and block the effects of chemotherapy.
KCL-HO-1i, created at King’s College London (KCL), targets this protein to make tumours more responsive to treatment.
What will it treat?
Early tests on mice found the drug made breast cancer tumours more responsive to different types of chemotherapy, but it could translate to other forms of cancer as well. Miraz Rahman, a professor of medicinal chemistry at KCL, says: “If human trials are successful, KCL-HO-1i could become a valuable companion drug to existing cancer therapies – helping more patients to benefit from the treatments that are already available and reduce the need for more aggressive cancer therapies in the future.”
When will it be ready?
Researchers are now hopeful that trials involving patients with breast cancer and other forms of the disease could begin within two years.
Vaccines that can cure cancer – and prevent it coming back
What are they?
We tend to think of vaccines as treatments we have when we are well. They teach the immune system to recognise a virus so it is destroyed before it can make us sick – or at least make us less sick than we would otherwise be.
However, cancer immunisations are different. While some are being developed to prevent the disease in high-risk patients, most are given when a person has been diagnosed. And they are bespoke treatments, tailored to the patient’s own unique cancer.
Cancer vaccines may be able to cure even advanced, previously terminal cancers and stop cancer coming back and spreading after it has been treated.
Three out of four cancer deaths occur because cancer spreads to other organs, which often happens after a period in which stray cancer cells go to “sleep”, becoming undetectable before waking up and forming tumours.
A cancer vaccine not only trains the immune system to recognise and fight off the initial cancer, but also teaches the immune system to recognise any stray cells so they can be picked off if they become active.
“The key to effective anti-cancer treatments is to create an immunological memory response,” said Prof Harrington. “We want the patient to have a standing army of immune cells trained to recognise and kill cancer if it wakes up.”
There are several different types of cancer vaccines in development which all work in slightly different ways. Many employ the mRNA technology used to create Covid vaccines.
What will they treat?
More than 20 mRNA-based vaccines entered clinical trials by 2021 targeting hard-to-treat cancers including bowel cancer, pancreatic and the brain cancer glioblastoma. This month, over 100 people with advanced head and neck cancer will take part in another mRNA-based vaccine trial.
When will they be ready?
One patient, a 55-year-old lecturer with bowel cancer, has already become the first to take the vaccine. In a national first, father-of-four Elliot Phebve received the developmental jab at University Hospitals Birmingham NHS Foundation Trust, one of several sites taking part in the colorectal cancer vaccine trial sponsored by BioNTech SE.
Meanwhile this month, the NHS announced that patients in England with head and neck cancer will be fast-tracked onto a clinical trial for a “potentially transformative” new vaccine. The first patients have already received the jab with more set to be enrolled at their nearest NHS hospital. More than 100 patients with advanced forms of the disease will be matched to the trial, known as AHEAD-MERIT (BNT113), which will run at 15 hospitals over the next year.
In July last year, the Government signed an agreement with the pharma company to provide up to 10,000 UK patients with precision cancer vaccines by 2030.
The ‘Trojan horse’ therapy that destroys blood cancer
What is it?
The drug, called belantamab mafadotin, has been dubbed a “Trojan Horse” therapy because it tricks cancer cells into absorbing it before killing them from within. An advanced form of chemotherapy, it can halt the advance of multiple myeloma (an aggressive type of blood cancer) for nearly three times longer than current therapies. The treatment was developed in the UK and is set to be rolled out to thousands of NHS patients in England. The health service is the first in the world to make the drug available to people with multiple myeloma.
However, side effects can cause blurry vision and other eye symptoms, including ocular toxicity, difficulty seeing clearly, dry eyes and photophobia. Patients must undergo regular eye tests and routine ophthalmological assessments before starting treatment and after each of the first three treatments.
What will it treat?
While multiple myeloma is incurable, the treatment is designed to extend people’s lives as much as possible while minimising the impact of side effects on quality of life. Around 1,500 patients a year in England will benefit from the treatment, which was approved by the National Institute for Health and Care Excellence. The drug will be offered to patients whose cancer has progressed or has not responded to the first choice of treatment using another drug, lenalidomide.
Patients who are prescribed the drug will receive it via an infusion once every three weeks in combination with two other cancer treatments.
Prof Peter Johnson, NHS England’s national clinical director for cancer, says the “life-changing” drug “has the potential to keep cancer at bay for years longer, giving people the chance of more precious time with friends and family”.
When will it be ready?
NHS England is fast-tracking access to the treatment for patients from today, through immediate funding via the Cancer Drugs Fund. Eligible patients will be treated via an infusion every three weeks in combination with other cancer drugs, bortezomib and dexamethasone.
The ‘revolutionary’ DNA blood test
What is it?
In a world first, the NHS will roll out liquid biopsies for patients with suspected lung cancer and women with breast cancer who haven’t responded to previous treatment. This blood test detects tiny fragments of tumour DNA in the blood, allowing clinicians to rapidly identify genetic mutations driving cancer, and match patients with targeted therapies tailored to a tumour’s genetic profile.
Experts say these advances will allow for “live monitoring” of both disease and treatment – meaning faster diagnoses and fewer side effects. The NHS will become the first health service in the world to roll out a “blood test-first” approach to diagnosing lung cancer, with health chiefs hailing it the “golden key” to unlocking personalised medicines.
What will it treat?
The rapid test could benefit up to 20,000 patients each year – 15,000 with suspected non-small cell lung cancer who have suspected stage three or four cancer after a CT scan, and 5,000 women with advanced breast cancer which is not responding to treatment. The hope is they might respond to drugs which can slow or halt the progress of disease.
It will be offered to non-small cell lung cancer patients after a CT scan shows signs of disease. Whilst it isn’t a replacement for tissue biopsies, it could help patients begin targeted treatment up to two weeks earlier, whilst waiting for results. In some cases, it will allow patients to avoid further tests or even chemotherapy altogether, as medics can narrowly focus treatment to be as specific as possible, meaning it’s “kinder” on the body.
When will it be ready?
Following a successful pilot, the roll-out begins this year for patients with suspected lung cancer and advanced breast cancer. It could then expand to cover six types of cancer.
Results from pilot NHS schemes for lung cancer show the approach can fast-track patients to start treatment two weeks earlier, and avoid repeated scans, delays and needless toxic therapies.
Prof Peter Johnson, the national clinical director for cancer at NHS England, says the approach could have more potential in the future, as it may be able to screen apparently healthy patients for signs of disease, too.
The pill that stops lung cancer in its tracks
What is it?
A daily pill, called lorlatinib, could stop cancer from spreading in lung cancer patients.
Trial results suggest that it works for at least five years in 60 per cent of patients, including just over half of the participants whose cancer had already spread to the brain by the time they joined the trial.
For comparison, an alternative cancer growth blocker crizotinib (branded as Xalkori and offered to some NHS patients) works in just 8 per cent of patients for five years.
Researchers have been unable to calculate exactly how long lorlatinib typically works for because most study volunteers have not seen their cancer progress since they began taking the medication.
Cancer experts say the results are “a really major step forward in lung cancer care”.
What will it treat?
It was trialled in patients who have ALK-positive lung cancer, which stands for anaplastic lymphoma kinase. ALK is a gene that is “switched off” in the womb but can turn back on for some people and cause cancer.
Around 49,000 people are diagnosed with lung cancer in the UK each year but only around 350 people have the ALK-positive type.
When will it be ready?
Lorlatinib is already available on the NHS but only for patients who have not had success with other treatments, but is only given to around 80 patients a year. The pill costs around £167 per day based on its list price.
It was rejected for wider use last year by spending watchdog, the National Institute for Health and Care Excellence (Nice), owing to a lack of evidence but could be reconsidered soon in light of the new data.
The breast cancer prevention treatment
What is it?
Anastrozole is a type of drug called an aromatase inhibitor. It cuts down the amount of the hormone oestrogen that a patient’s body makes by blocking an enzyme called aromatase. Oestrogen can stimulate the growth of some cancers in the body.
Anastrozole is already licensed in Britain as a treatment for breast cancer, but now its licence has been extended to be used as a preventative measure.
What will it treat?
NHS England said the drug will be available for post-menopausal women at moderate or high risk of breast cancer. They will include women with a family history of the disease, or who have faulty genes such as BRCA1, the so-called Angelina Jolie gene, that put them at greater risk.
Studies have shown that anastrozole can nearly halve the chances of breast cancer if taken daily for five years.
“If post-menopausal women are concerned about their breast cancer risk because of their family history, it’s best they speak to their GP to decide whether this treatment is appropriate,” said Melanie Surtevant, Associate Director of policy, evidence and influencing at Breast Cancer Now.
When will it be ready?
The drug is available now. It’s been recommended since 2017, but uptake has been low. However, the fact that it is now licensed for prevention should lead to an increase.
The tumour annihilator
What is it?
The AOH1996 drug is named after Anna Olivia Healy, who was born in 1996 and died aged nine after being diagnosed with neuroblastoma, a rare childhood cancer affecting the nerves.
Researchers in the US have developed a molecule that “appears to annihilate all solid tumours” in preclinical research – while leaving healthy cells unharmed.
The experimental cancer-killing pill is taken twice a day and blocks a protein called proliferating cell nuclear antigen (PCNA). In a mutated form, PCNA is critical to the growth and repair of tumours.
“PCNA is uniquely altered in cancer cells, and this allowed us to design a drug that targeted only the form of PCNA in cancer cells, killing tumours while leaving healthy cells untouched,” said Prof Linda Malkas of the department of molecular diagnostics and experimental therapeutics at the City of Hope Hospital, Los Angeles.
What will it treat?
PCNA is found in all cancers, and AOH1996 has shown promise in 70 cell lines, including breast, prostate, brain, ovarian, cervical, skin and lung cancers. It is now being trialled in people for whom standard treatments, such as chemotherapy, have not worked.
When will it be ready?
Prof Harrington said that the drug is “extremely promising”. However, AOH1996 has only just entered phase 1 human trials.
“Even with accelerated trials and evaluation to test AOH1966 for safety and effectiveness, the treatment will take at least five to 10 years to gain approval in the UK,” he said.
A drug to supercharge your immune system
What is it?
Immunotherapy, which harnesses the power of our immune system to attack cancer, has revolutionised cancer treatment.
Nicholas Turner, a consultant medical oncologist at The Royal Marsden NHS Trust and professor of molecular oncology at The Institute of Cancer Research, said: “Twenty years ago, metastatic melanoma [skin cancer that has spread to other organs] had an average survival of around seven months with virtually nobody cured.
“Today, thanks to immunotherapy, survival rates are around 40 per cent.”
But cancers are wily: they can reach out to press “off switches” on our immune cells, calling off their attack. As a result, said Prof Harrington, cures occur in “far too few patients”.
New drugs called “checkpoint inhibitors” block cancer’s ability to hit off switches on the immune system. The best-known checkpoint inhibitors target an off-switch protein called PD-1.
Prof Harrington said: “The problem is that there are dozens of these ‘off switches’. If we find a way to block one, cancer will find another. We need drugs to back cancer into a corner by blocking all the ways it turns off the immune system.”
A new drug, relatlimab, blocks an off-switch protein called LAG-3, making immunotherapy likely to work on more people and more types of cancer.
What will it treat?
Opdualag, a new drug which combines relatlimab with a PD-1 checkpoint inhibitor called nivolumab (Opdivo), has recently been approved by the US Food and Drug Administration for advanced melanoma which cannot be removed by surgery or has spread to other parts of the body.
Other drugs targeting LAG-3 are being trialled for the treatment of multiple myeloma, oesophagal and gastric cancer, among other types of cancers. Opdualag is also being studied in clinical trials of other cancers, including lung, colorectal and liver cancer.
When will it be ready?
The National Institute for Health and Care Excellence approved nivolumab-relatlimab within the NHS for people 12 years and over who have untreated, advanced melanoma last year, with more approvals expected in the coming years.
Flash radiotherapy
What is it?
Radiotherapy is often considered an old-fashioned treatment. It uses X-ray energy to kill cancer cells but can also burn and damage healthy tissue in vital organs such as the brain and heart.
However, in flash radiotherapy, radiation is delivered a thousand times faster than in conventional radiotherapy.
A therapeutic dose can be given in a fraction of a second. This intensity damages the DNA in cancer cells but is up to 50 per cent less damaging to normal cells.
Cancer Research UK-funded scientists in the UK have found that flash radiotherapy speeds up oxygen use in the tissues being treated. In normal cells, this creates a condition called hypoxia, and this protects the normal cells from DNA damage.
This protection means clinicians could potentially increase radiation doses to levels that would cause unacceptable side effects with conventional radiotherapy.
What will it treat?
In future, flash could be used for hard-to-kill cancers in the brain, lungs or gastrointestinal area, where healthy tissue surrounding tumours is particularly vulnerable to damage from radiation exposure. “The potential is enormous,” said Dr Bromley.
When will it be ready? So far, flash radiotherapy is only being used in trials. Dr Bromley added: “It could take as long as 10 years before flash becomes routine.”
Super-viruses that can infect cancers
What is it?
What could be cleverer than giving cancer a disease? That’s the premise of a new breed of engineered viruses created to infect cancer cells but not healthy ones. The viruses essentially trick cancer tumours into destroying themselves.
First, the virus is injected directly into tumours. It then hijacks and replaces the tumour DNA to replicate itself. As the virus grows within cancer cells it bursts them open, and then spreads to other cells while also prompting the immune system to combat the cancer throughout the body.
A new therapeutic virus, RP1, has been created from the herpes simplex virus, which causes cold sores. Tumours are categorised as “hot” or “cold” depending on how much they trigger an immune response. Melanoma is “hot” while breast, pancreatic and prostate cancers are “cold”.
RP1 is designed to work on “hotter” tumours, including in patients for whom immunotherapy hasn’t worked. Sister viruses RP2 and RP3 have been designed to treat more immunologically “cold” tumours.
What will it treat?
In trials, researchers have used an engineered virus to make immunotherapy more effective on brain tumours. It is also being trialled on patients with organ transplants who often develop skin cancers. A quarter of patients saw their cancer disappear.
It has also been trialled in the UK on a small number of last-chance patients with advanced cancers including skin, eye, oesophageal and head and neck cancer. All had failed to respond to other treatments, including immunotherapy.
A quarter saw their cancers shrink and one patient with salivary gland cancer saw his tumour disappear completely. He remains free of cancer 15 months after starting treatment.
When will it be ready?
Availability will depend on the benefit of treatment and the cost of therapy. “In the next three to five years, RP viruses could be available to NHS patients,” said Prof Harrington.
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