Less deadly than you think
The world is making impressive progress averting cancer
And there are more improvements to come
Illustration: Eiko OjalaIT IS ALREADY a frightening disease, and one that, on the face of things, is becoming ever deadlier.
Cancer kills perhaps 10m people a year, a number that has been rising steadily over the decades.
In rich countries, half of men and one in three women develop it at some point.
In many countries, including Australia, Britain, Canada and Japan, people are more likely to die of cancer than of any other cause.
Yet these scary numbers are largely a function of demography.
As the world’s population grows, so does the number of deaths from cancer.
The rising median age of people around the world has the same effect, since cancer can take decades to develop and therefore afflicts the elderly more than the young.
Strip out the effects of population growth and ageing and the rate of deaths from cancer has actually fallen markedly over the past 30 years or so (see chart 1).
Cancer is becoming much less deadly—and scientists’ fast-improving understanding of the disease holds out the prospect of further advances for years to come.
The declining mortality rate reflects all manner of improvements in prevention, diagnosis and treatment.
The biggest gains have come from reductions in smoking, which causes around 85% of lung cancers and 20% of all cancer deaths globally (see chart 2).
Mammograms, colonoscopies and cervical smear tests, among other forms of screening, have helped to identify lesions, polyps and other tissue that may develop into cancer, but that can be removed, preventing any such progression.
Better surgical techniques and cancer medicines have improved survival rates for those who do develop the disease.
In recent years immunotherapy, in which the immune system is induced to fight cancer more effectively, has also made big strides.
By one estimate, such advances averted nearly 6m deaths in America between 1975 and 2020 from lung, breast, bowel, prostate and cervical cancer, which collectively accounted for around 70% of cancer deaths in the late 1970s.
Just over half of the averted deaths were the result of reduced smoking.
Another 23% stemmed from better screening and 20% from improvements in treatment.
Stomach cancer, once common in rich countries, has also declined sharply.
In the 1990s researchers established that it was often caused by Helicobacter pylori.
Infections of the bacteria were already declining, owing to improvements in hygiene and greater use of antibiotics since the 1950s, but the discovery spurred testing and direct treatment of them, further reducing the incidence of stomach cancer.
One down
Perhaps the most striking breakthrough concerns the prevention of cervical cancer.
In the early twentieth century, it killed more women in America than any other form of the disease.
The first headway against it came with the realisation that certain changes in the cells in the cervix, visible under a microscope, often progressed to cancer.
This led to screening programmes to detect and remove suspect tissue before it turned cancerous.
Studying the many samples collected in this way led to the discovery that almost all cervical cancers were caused by infection with the human papillomavirus (HPV).
The subsequent development of HPV vaccines holds out the prospect of the near-eradication cervical cancer.
In Britain the vaccine has led to a 90% drop in cervical-cancer cases for women in their 20s, based on data for the first cohort that was offered the jab at the age of 12 or 13.
The success in curbing lung and cervical cancer has become a template for scientists looking for ways to prevent other types of cancer.
It has taught them first to identify who is at greatest risk of developing cancer and then to intervene in whatever way works best: getting smokers to quit, getting young women vaccinated against HPV.
Most cancers, admittedly, are harder to tackle, since their causes are more complex and less well understood.
In fact, only around half of all cancer cases can be explained by a known risk-factor for the disease.
But the wealth of tissue samples collected over the years, along with advances in cellular biology, are slowly making it easier to identify patterns and tailor treatments accordingly.
Several new vaccines developed in this way are already in the works.
Such data are helping identify prophylactic drugs, too.
The hope is that, rather than treat cancer once it has developed, many forms of the disease can be stopped from developing to begin with.
A long runway
“Cancer does not come out of nowhere,” explains Sarah Blagden of Oxford University: it slowly develops over many years, providing ample opportunity for medical intervention.
The process starts when genetic mutations cause normal cells to reproduce in ways they should not.
As they divide, some of these abnormal cells develop features that help them to hide from the immune cells that normally clear out damaged and diseased cells.
The abnormal cells eventually form clumps of tissue called lesions, polyps or tumours.
These lesions can take 5-15 years to develop.
Once they are big enough, they can be spotted by mammograms, colonoscopies and the like.
Some stop growing or shrink, but others develop into fully fledged cancer, meaning that they begin to protrude outside the organ where they first started growing and will eventually metastasise, or spread around the body (although that can take a further 5-10 years).
Most cancer-screening programmes aim to detect lesions and remove them before they become cancerous.
But it is hard to know whom to screen and which lesions, once detected, to remove.
Screening tends to be based on very broad criteria, such as age or having a close relative who has had cancer.
As a result, many people who are not at high risk undergo unnecessary tests, including invasive procedures that can cause harm.
Colonoscopies, for example, can perforate the colon; biopsies of breast, lung or other tissues can cause infections and other complications.
What is more, only about 25% of the most common type of lesion found in breast tissue turn cancerous.
By the same token, although the majority of bowel cancers start from polyps, only 5-10% of polyps develop into cancer.
Scientists at University College London have discovered that, if left alone, 30% of a particular type of lesion in the lungs regress over time.
All such lesions, however, are treated as incipient cancer because there is no way to predict with certainty whether they will turn malignant.
The result is lots of unnecessary, expensive and debilitating surgery, radiation therapy and chemotherapy.
One solution to the problem of side-effects from testing would be cheaper, less invasive screening methods for lesions—and many are indeed in development, including various breath, blood or urine tests.
Better still would be to find more accurate indicators of who is at risk, to target treatment to those who really need it.
Scientists have been making progress in this area, too, in two ways: by identifying genetic predispositions and by working out what proteins in blood or tissue might serve as “biomarkers” of a heightened risk of developing cancer.
Some 5-10% of cancer cases appear to have genetic origins.
About one in every 200 people has faults in genes called BRCA-1 and -2 that are involved in suppressing cancer, for example.
For women such mutations carry a 60-80% risk of developing breast or ovarian cancer.
One in 300 people has Lynch syndrome, which is caused by mutations in genes involved in DNA repair.
These people have a 40-80% chance of developing colorectal, endometrial and other types of cancer.
These are extreme cases, but many other genes appear to heighten the risk of developing certain cancers.
Since genes are inherited, it is easy to know who to screen for such mutations and then monitor more closely for signs of disease.
Another set of clues about who is at risk comes from big medical studies conducted in recent decades to examine links between diet, lifestyle and cancer.
Some of them, such as the EPIC project, which has tracked 500,000 Europeans for nearly 30 years, have created “biobanks” of blood samples.
That allows researchers to examine blood from participants who later developed cancer, and to compare it with samples from those who remained healthy, to see if there are any distinguishing features.
In particular, they have been looking for proteins that are more common among future cancer patients.
Such research has found that people with high levels of insulin-like growth factor (a protein that tells cells to grow) are at higher risk of breast and bowel cancer.
Biobank samples also helped a team led by Marc Gunter from Imperial College London identify new proteins that seem to be biomarkers of an elevated risk of breast cancer.
“They’ve come completely out of the blue, in a way,” he says.
These discoveries are not only useful in themselves, but can also be combined with other data to produce more refined measures of risk.
Genetic screening, blood tests, information about diet, exercise and so on can all be fed into “multimodal” cancer-risk calculators that have entered clinical practice in the past five years.
Doctors use them to decide, for example, who should have earlier breast-cancer screening or take cancer-prevention medicines.
Rapidly improving technology is helping refine these risk models.
It is now possible to test a single blood sample for thousands of proteins rather than the two or three that would have been the maximum a decade ago.
Researchers are investigating whether AI can improve risk-prediction by spotting subtle patterns in mammograms or whole-body scans.
The development of single-cell transcriptomics, a technology that analyses gene expression at the cellular level, has made it possible to see how cells in a tissue sample interact with each other.
(Previously, the extraction of DNA involved mincing a tissue sample, losing information about individual cells.)
This and other new analytic methods have yielded detailed information about how immune cells function, for example, or about how proteins indicative of cancer can be detected—the sort of information needed to develop preventive drugs and vaccines.
A research group led by Walid Khaled at Cambridge University has discovered, for instance, that immune cells in the breasts of healthy women who carry BRCA mutations are as ineffective as those found in women with advanced breast cancer.
The next step, says Dr Khaled, would be to identify therapies that can reinvigorate these cells.
Better than cure
Vaccines are another field that has progressed “tremendously fast” in the past decade, says Nora Disis of the Cancer Vaccine Institute at the University of Washington.
“We have a much better idea of the type of immune response we need to eradicate the cancer,” she says.
Five years ago, says Dr Disis, her institute was focusing almost exclusively on vaccines used as a treatment for advanced cancer.
Now, she says, about half of the institute’s work is on preventive vaccines.
Several research groups and biotech firms in America and Europe are testing preventive jabs for breast, colon and other cancers in patients who are at high risk of the disease (such as those with BRCA gene faults, Lynch syndrome or pre-cancerous lesions).
These jabs are still in early trials.
The first results, showing whether they reduce the recurrence of polyps or other lesions, are expected in three to five years.
In the past, says Olivera Finn of the University of Pittsburgh, there were fears that jabs given to people before cancer had developed might spur the immune system to attack healthy cells.
But experience in patients with late-stage cancer (for whom the potential life-saving benefits outweighed that risk) showed that such fears were misplaced.
The immune system, it turns out, is pretty good at focusing just on the cancer cells.
Unlike individualised therapeutic cancer vaccines, which are often tailored to an individual patient’s specific cancer mutations, preventive jabs should work for a broad range of patients.
In one of the largest clinical studies on how lung tumours evolve, scientists at the University College London discovered that the lung cells of smokers develop specific changes linked to cancer years before the cancer occurs.
Researchers at Oxford have developed a vaccine targeting those changes which is due to start clinical trials next year.
A preventive vaccine developed by Nouscom, a Swiss biotech company, uses what its developers call a “brute force” approach: the jab targets 209 different fragments of molecules found in pre-cancerous and cancerous tissue but not in healthy tissue.
The first round of clinical trials, reported in April, showed it successfully induces the immune system to target cancer cells, at least in tests in Petri dishes.
Also in clinical trials is a vaccine for bowel cancer prevention.
In 2023 Dr Finn’s group reported preliminary results from a vaccine targeting a protein called MUC1, found in 80% of all types of cancers.
Although the vaccine prompted an immune response only in a sub-category of people with colon polyps, that group saw a 38% reduction in polyp recurrence within a year.
The granularity of data available from big clinical studies is also hastening the identification of drugs that may help prevent particular forms of cancer in specific populations.
Researchers have noticed, for example, that people who take aspirin to prevent heart attacks or metformin to treat diabetes have reduced rates of cancer.
Clinical trials showed that anastrozole, a drug used to treat breast cancer, halves the risk that some post-menopausal women will develop it in the first place, prompting Britain’s drug regulator to approve it for prophylactic treatment in 2023.
There are now studies investigating whether such drugs can be given in ways that reduce their negative side-effects, such as intermittent dosing or applying them topically or via injection only to the tissue of concern.
And there is hope that GLP-1 receptor agonists such as Ozempic, wonder drugs with all sorts of benefits beyond their original use to manage diabetes, might also help prevent certain forms of cancer.
Some of these therapies benefit only relatively narrow groups.
In 2023 researchers found that metformin can reduce the recurrence of cancer for women treated for one particular form of breast cancer, accounting for about 20% of cases, but not for other types.
Such results, showing benefits for specific sub-groups of patients, are starting to be seen as the norm in the search for preventive therapies for cancer, says Andrew Chan of Harvard University: “It is very unlikely the future will be around something one-size-fits-all.”
Involved but not intractable
The complexity of cancer, with its bewildering variety of forms, makes devising treatments difficult.
Developing vaccines or testing preventive drugs for a disease that can take 15 years to develop is by its very nature a time-consuming task.
These obstacles explain why progress against cancer tends to come incrementally, rather than through attention-grabbing breakthroughs.
The sweeping benefits of broad public-health measures, such as reducing smoking or improving food hygiene, have already been reaped, at least in the rich world.
Developing future preventive treatments by matching sub-categories of patients with a shifting constellation of therapies will inevitably involve a lot of trial and error.
But scientists are making steady headway in narrowing down the pool of people at risk and tailoring treatments to them.
And because this process is continuous and open-ended, it will go on yielding benefits for decades to come.
Cancer has already become a much less deadly disease than it was 30 years ago.
Thirty years from now, it will almost certainly be much less deadly than it is today.
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