The brain: barrier and sanctuary

A small ultrasound device implanted in the skull can be switched on at each chemotherapy visit to briefly open the brain barrier, letting drugs in every cycle.

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.

Up to a fifth of people with advanced solid tumours have cancer in the brain and are usually barred from trials. Letting in those whose brain disease is treated, stable or symptom-free would widen trials and tell us whether drugs work in the brain.

Drugs that reach brain tissue may still fail to reach the fluid where cancer spreads along the linings. A lab model of that second barrier would let us screen for drugs that cross it.

Cancer spreading along the linings of the brain is almost untreatable. Injecting engineered immune cells directly into the brain fluid, through a small reservoir, reaches it.

The nerves at the top of the nose lead directly into the brain, bypassing the barrier. Nasal delivery of drugs, and even immune cells, has worked in animals.

New drugs that destroy cancer proteins are usually too big to enter the brain. Making much smaller versions could bring this approach to brain tumours.

Interleukin-12 is one of the most powerful immune stimulants but is too toxic to inject into the bloodstream. A virus can be engineered to make it only inside a tumour.

Engineered immune cells given by drip rarely reach brain tumours. Briefly opening the barrier with focused ultrasound at the right moment may let them in.

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.

Fluid taken from the lower back contains DNA from brain tumours. Testing it can diagnose, monitor and detect resistance without brain surgery.

Whether a drug gets into the brain is measured early in development but rarely published. Making that number public would show which existing drugs could treat brain disease.

Pumping drugs slowly through fine tubes into a brain tumour can bypass the barrier, but the fluid often leaks away. Robotic placement and live scans would show where it actually goes.

One in five people with advanced cancer has brain spread, yet most trials refuse them. Requiring brain cohorts would give those patients evidence instead of guesswork.

A fifth of patients with solid tumours develop brain metastases and are usually excluded from trials. This would fund a programme that studies and treats them as a disease in their own right.

Brain tumours shed very little DNA into blood, so a sonobiopsy briefly opens the brain's barrier with focused ultrasound to release enough to read from a blood sample.

The brain has natural transport doors for iron. Attaching a key that fits those doors can smuggle large drug molecules in, a trick now working in Alzheimer's medicines.