Bottlenecks of the war on cancer

Nearly every targeted therapy stops working within months to a few years as the tumour adapts.

Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.

Records, scans, genomes and outcomes sit in separate systems that cannot talk. Every patient's experience is lost to the next.

After a 'successful' treatment, cells can sleep for years then relapse. We can barely detect them and cannot target them.

The system pays the same for a drug that adds two months as for a cure, so companies race to copy rather than to cure.

Nine in ten cancer drugs that work in mice fail in humans. Our models are the reason.

Metastasis causes about nine in ten cancer deaths but gets a small fraction of research money and almost no trials of its own.

Seven in ten cancer deaths happen in low- and middle-income countries, where radiotherapy, pathology, surgery and drugs are scarce.

There are guidelines saying what a survivor should have checked and when. There is usually no mechanism that tells an individual survivor, ten years out, which checks they are due this year, or anyone whose job it is to notice they were missed.

Around four in ten cancers are preventable with tools we already own: vaccines, tobacco control, weight, alcohol, sun and infection control.

New cancer drugs routinely cost over $150,000 a year, often for months of benefit. Systems cannot afford them and patients go bankrupt.

Cancer registries are good at incidence and mortality and record almost nothing about late effects, so the scale of the problem is estimated from a handful of cohorts rather than counted. Europe cannot say how many survivors it has.

The interventions with the best evidence after cancer are supervised exercise, psychological therapy and specialist rehabilitation. The commonest finding across this whole front is that the evidence exists and the service does not.

Screening exists for only a few cancers. Pancreatic, ovarian, liver, oesophageal and most lung cancers are found when cure is unlikely.

The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.

A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.

Fewer than one in ten adults with cancer joins a trial. Trials close for lack of patients, not lack of ideas.

Every tumour is a population of genetically distinct clones: in multi-region sequencing of kidney tumours, roughly two thirds of mutations were missing from at least one region. Treatment kills the dominant clones and leaves resistant minor clones to grow back, yet a single diagnostic biopsy is still treated as the whole disease.

Thousands of cancer AI models are published; a handful are in clinical use, and fewer have shown they help patients.

Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.

Cancer cachexia, the muscle and fat wasting driven by tumour and host inflammatory signals, affects most patients with advanced pancreatic, gastric and lung cancer, and treatment-limiting toxicities decide what dose a patient can receive. Only Japan has an approved cachexia drug, and supportive care research gets a small share of funding relative to its effect.

Negative trials, failed drugs and abandoned programmes are rarely published, so the same mistakes are repeated.

Patients fall between specialists, wait for referrals and often do not get the treatment guidelines say they should.

Research money follows visibility, not burden: breast, prostate and leukaemia receive far more funding per death or year of life lost than lung, pancreatic, liver, oesophageal, gastric, bladder and uterine cancers, and metastasis research gets an estimated 5% of funding despite causing most deaths. Advocacy strength and peer review that rewards mechanism explain the skew.

Most people who carry a high-risk cancer gene do not know it until they or a relative gets cancer.

Knowledge diffusion is slow: it takes years for a proven result to change what most patients receive, and no one can keep up with the literature.

Cell therapies take weeks to make for one patient and cost hundreds of thousands of dollars. Isotopes run short.

Old, cheap drugs with anti-cancer signals never get the trials they need because no one profits from the result.

Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.

Survivors are screened for second cancers on the strength of how large their risk is, not on the strength of a trial showing that screening them saves lives. For most organs there is no programme at all.

The memory and concentration problems after chemotherapy and cranial radiotherapy are real and measurable. Every drug tested against them has failed, including one tested properly in 276 people, and nothing restores lost processing speed.

Cancer treatment measurably accelerates several markers of biological ageing. No trial has ever asked whether moving one of those markers makes any difference to a person, and an entire retail industry rests on the assumption that it would.

The number of people with cancer is rising faster than the workforce trained to treat them.

Most people with cancer are over 65 but most trial patients are younger and fitter. We guess how to treat the majority.

Finding more cancer is not the same as saving lives. Screening also finds cancers that would never have hurt anyone, and treats them.

Most people who die of cancer worldwide do so without adequate pain relief.

Most patients cannot understand their options, find trials, or push back, so decisions are made for them.

Fewer than half of landmark cancer biology findings reproduce when someone else tries.

Taken together rare cancers are a fifth of all cancers, but each one alone is too small for a company to invest in.

Regulatory divergence means a drug approved in one country can take years to reach another, or never arrive.

Companies with complementary drugs rarely test them together, and data that could answer questions stays locked up.

Surgery and radiotherapy cure more people than drugs do, but attract a fraction of the research investment.

The blood-brain barrier's tight junctions and efflux pumps keep antibodies, antibody-drug conjugates and most kinase inhibitors out of the brain, so glioblastoma treatment has barely changed since 2005 and brain metastases, which develop in about a fifth of adults with cancer, are usually left to radiotherapy alone.

On subject after subject here, the studies exist and cannot be combined, because each used a different definition, a different questionnaire or a different threshold. A prevalence that ranges from 0 to 84 per cent is a measurement problem, not a biological one.

A second cancer after radiotherapy can take forty years to appear. Immunotherapy and antibody-drug conjugates have been in first-line use for a few. Being told a new drug has no late effects usually means nobody has been followed long enough to see one.

Most academic discoveries die before anyone tests them in people because nobody funds the middle step.

There are thousands of possible drug pairs and sequences. Trials can test a few dozen a year.

Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.

Older, Black, Hispanic, Asian, rural, poor and multimorbid patients are under-represented, so results may not apply to them.

We do not reliably know what happens to patients after approval, so we cannot tell which drugs deliver in practice.

Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.

Patients are sold unproven treatments and frightened away from proven ones.

After a transplant or intensive chemotherapy, the part of the immune system that makes new kinds of T cell recovers slowly in adults and sometimes not at all. The deficit is well described, well measured and currently not correctable.

Tens of millions of people live after cancer with heart damage, infertility, second cancers and fear, and few services.