Clonal evolution

Instead of hitting a tumour with the maximum dose until it stops working, adjust the dose to keep the tumour small and let drug-sensitive cells suppress resistant ones. Test this properly across several cancers.

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.

After surgery or curative treatment, everyone gets regular blood tests for leftover cancer DNA, and the pooled results power forecasts of who will relapse and trials of acting early.

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.

Rather than giving the same dose until the cancer grows, measure tumour DNA in blood every few weeks and let a validated algorithm raise, lower, pause or switch drugs to keep the cancer suppressed for longer.

When a scan shows most tumours shrinking but one growing, that odd lesion holds the escape mechanism. Sampling it, and treating it locally, should be routine.

Most stage II patients never relapse, yet all are offered a year of immunotherapy. Use a blood test to treat only those with detectable residual disease.

Track FGFR2 resistance mutations in blood and switch to the next-generation inhibitor that still covers them, before the scan shows progression.

If a blood test reliably shows whether cancer will come back after surgery, trials could use it instead of waiting years for relapse. Regulators have a process to bless such a test; oncology should use it.

When a treatment stops working, the tumour is rarely re-sampled, so nobody learns why. Paying for a biopsy at that moment would build the missing map of resistance.

Blood tests can now find leftover cancer months before scans, but most patients who test positive have nothing to enrol in. One standing trial per country would fix that.

Use a blood test after surgery to decide who gets chemotherapy: spare the negatives, and find something that actually works for the positives.

Give adjuvant treatment by the tumour's molecular class rather than by stage and grade: nothing for POLE-mutated, immunotherapy for MMRd, chemotherapy plus targeted agents for p53-abnormal, hormones for NSMP.

A Japanese trial found vitamin D supplements did not help everyone after digestive cancer surgery, but appeared to help a subgroup identified by a tumour marker. That subgroup deserves its own trial.

Blood tests can already detect tumour DNA. Reporting which sub-populations of the tumour are growing or shrinking, cycle by cycle, would turn the test into an evolution monitor.

Between diagnosis and surgery there are usually a few weeks. Giving a new drug in that window and comparing the tumour before and after surgery shows whether it hits its target in real people, quickly and cheaply.

Once a year, send the same blinded blood samples to every company selling a tumour-DNA test and publish how each performed.

Trials often measure a stand-in for survival, such as time until the cancer grows on scans. An independent body would test, for each cancer and treatment type, whether the stand-in actually predicts survival, and publish the answer.

Companies and public funders would pool money and scientists to crack the hardest cancer proteins, such as MYC and mutant p53, sharing everything openly until there is a real drug candidate, then competing on the final product.

Sleeping cancer cells survive by recycling their own contents. An old malaria drug blocks that recycling and is being tested in people with no visible cancer but detectable residual cells.