Metastasis is understood least and studied last

Governments and foundations would pool a prize of about a billion dollars into an escrowed fund, paid only when a treatment is shown in a well-controlled registration cohort to keep most patients with a currently incurable metastatic cancer, such as pancreatic adenocarcinoma or glioblastoma, disease-free for five years. The winner keeps its patent but accepts a price ceiling.

Before cancer spreads, distant organs are changed to become welcoming. A test for those changes would show which organ is at risk while a person still looks cancer-free.

Almost all cancer deaths are caused by spread, yet metastatic tissue is rarely studied because rapid autopsy programmes exist at only a handful of centres. A funded 20-site network with one protocol, one consent framework and open sample access would collect donated tissue within hours of death.

When patients who agreed in advance die of cancer, sampling every tumour within hours reveals how the disease evolved and escaped every drug. Few hospitals can do this today.

Today a cancer drug is approved for shrinking tumours. A drug that stopped cancer spreading would fail that test, so almost nobody develops one. A new endpoint would fix that.

Metastasis causes about nine in ten cancer deaths but gets a small slice of research money. This would ring-fence a tenth of national cancer research budgets for the biology and trials of spread itself.

Most cancer drugs cannot cross into the brain. Combine ultrasound that briefly opens the barrier with drugs engineered to be carried across, and make this a standard platform for every brain tumour and brain metastasis.

Some people have only a few sites of spread and can be treated at each one; others have further deposits not yet visible, and counting lesions cannot tell them apart. A signature built from tumour DNA levels, microRNA classifiers and clonal diversity across lesions would define the biology and spare futile ablation.

Different cancers favour different organs, and so do different patients. A model that predicts which organ is at risk could target surveillance and prevention.

Inflammation from infection, injury or surgery can wake dormant cancer cells. Interleukin-1 beta drives that awakening in mouse models of breast cancer, and a cardiovascular trial of the interleukin-1 beta blocker canakinumab saw fewer lung cancers, so blocking it early might keep dormant cells asleep.

Surgery makes some immune cells throw out sticky DNA webs that trap travelling cancer cells and help them settle. Dissolving those webs during the operation might prevent some relapses.

Cancer usually kills by spreading to bone, liver, lung or brain. Almost all laboratory models grow tumours under the skin instead, where the surroundings are nothing like those organs.

The stress of an operation may help stray cancer cells survive and settle. A few days of two cheap old drugs around surgery might reduce that risk.

Cancer cells travelling in the blood can be counted. If a drug clears them, that is an early sign it may stop spread, and it reads out in weeks rather than years.

Cancer spreading along the linings of the brain has no treatment that reliably controls it. Injecting engineered immune cells directly into the brain fluid, through a small reservoir, reaches it.

Many relapses come from cancer cells that hid dormant for years. Find drugs that either force them awake so chemotherapy kills them, or keep them asleep for life.

Sleeping cancer cells hide in bone marrow where drugs cannot reach them. Pushing them into the bloodstream on purpose, then treating, might clear them.

Drug tests normally use cells from the original tumour. Growing the rarer cells found in blood would test drugs against the cells that are actually travelling.

Breathing in an immune-activating drug could turn the lungs into bad soil for cancer seeds, at doses far too low to cause body-wide side-effects.

If we cannot kill sleeping cancer cells, we could try to keep them asleep for life. That would turn residual cancer into a harmless passenger.

Drug candidates are tested for shrinking tumours, almost never for stopping spread. A standard spread test would find anti-metastatic drugs we are throwing away.

Blood tests tell you which tumour sub-populations are growing; scans tell you which lesions are growing. Joining the two would tell you where to biopsy or irradiate.

Lung cancer spreads to the brain more than any other common cancer, and the newest drugs seem to stop it happening. Almost no trial is designed to prove that, so the claim stays a footnote.

Metastasis causes most cancer deaths, yet no drug is developed to stop cells spreading. Create a formal approval route for drugs that prevent metastasis, tested in people at high risk of it.

Surgical stress releases catecholamines and prostaglandins that suppress anti-tumour immunity and help metastatic cells seed. Phase 2 trials of a five-day course of propranolol plus etodolac around breast and colorectal surgery shifted tumour markers of metastasis and immune suppression in the right direction; both drugs cost cents, and a publicly funded phase 3 is the missing step.

Some cancers reach the brain in up to a quarter of patients. Prevention trials could aim specifically at stopping that, instead of treating it once it has happened.

The liver is where bowel cancer most often spreads. Drugs delivered straight into the liver's blood supply could retrain its resident immune cells to reject arriving cancer cells.

Spread causes around nine in ten cancer deaths but receives a small slice of research funding. A funding floor would change what gets studied.

Cancer cells need stiff, cross-linked tissue scaffolding to settle and grow in a new organ. Blocking the enzymes that build it may stop new colonies taking hold.

Cancer cells in the blood wrap themselves in platelets as camouflage. Aspirin may remove that cloak, and it is cheapest to test in the patients at highest risk of relapse.

Give a small number of scientists a decade of guaranteed funding to work on a single hard problem such as dormant cancer cells, with no pressure to publish quickly.

Intracavitary immunotherapy targets cancer that coats the lining of the abdomen or chest, which drugs given by drip barely reach. Delivering it straight into the cavity gives far higher local doses.

The first lymph node cancer reaches is also where the immune system learns to fight it. Injecting immunotherapy into that node before surgery, instead of removing it blindly, may work better.

Nearly half of women with metastatic triple-negative breast cancer develop brain metastases and survive under five months after the diagnosis, yet the trials that set the standard mostly exclude active brain disease. Requiring a brain metastasis cohort in every phase 3, with intracranial response as an endpoint, would answer whether the new drugs reach the brain.

A positive blood test tells you cancer is back but not where. Combining whole-body MRI with modern PET tracers may find a single spot that can be zapped.