Adaptive Chemotherapy

Remember the Borg on the Star Trek TV show? One reason they were such a formidable foe was that they adapted to attacks. When the Federation personnel from The Enterprise fired laser rifles at Borg soldiers the weapons were effective at first. Borg died, but the surviving ones learned from the loss and adapted to the laser gun, so they could survive subsequent Federation attacks. The Federation adjusted the frequency of their rifles and the Borg found a way to adapt to that tactic.

Cancer is similar. Many treatments fail because they effectively kill most of the malignant cells, but some survive – these cells are resistant to the drug – and when the cancer grows back most of the cells are resistant. Cancer is a dynamic ecosystem while the conventional treatment regimen is linear – a certain dose of a certain drug for a certain time.  Biologists know of the phenomenon of somatic evolution – the accumulation of mutations in the body’s cells.  This accumulation plays a part in the initiation of some cancers.  Even inside a tumor this evolution occurs as the cells are subject to natural selection forces.  Those forces can include attack by chemotherapy medicines.  It has also been found that some breast cancers can increase their sensitivity to estrogen if the patient takes aromatase inhibitors to lower estrogen levels in the body.

Adaptive therapy is a program of chemotherapy wherein doctors change the type and dosage of drug in an attempt to fake out the cancer. It is an alternative to the dose-dense regimens and metronomic regimens.

An article in the journal Cancer Research called adaptive therapy a system that “evolves in response to the temporal and spatial variability of tumor microenvironment and cellular phenotype.”

The insight that led thinkers to the idea of adaptive chemotherapy was that evolutionary principles are at work within the tumor. Tumors are heterogeneous – the cells are not all alike – and the cells are relatively genetically unstable, leading them to mutate over time and as the tumor grows. Different cells have different sensitivities to chemotherapy, and some are more resistant than others.

" "The idea is to treat the tumor as an ecosystem composed of a heterogeneous array of cells. Indeed, some scientific work suggests that a pre-cancer with a high Shannon index – this index is a measure of diversity – is more likely to develop into a full-blown cancer. A more diverse group of cells is better equipped to fight off the body’s immune system and chemotherapy treatment, too.

Both dose-dense and metronomic regimens involve fixed administration schedules. Adaptive therapy, which is based in theory on population ecology principles, can feature variation in both timing and dose sizes. The aim is to maintain a fixed population of cancer cells, so more of the drug is given if the tumor grows and less if the tumor shrinks.

Many see this method as a way to overcome the limits that conventional chemo regiments run up against.  Moffit Cancer Center’s Robert Gatenby was quoted as saying the maximum tolerated dose approach is “probably the worst way you could give cancer therapy.”

So far, adaptive therapy is not widely used in administration of chemotherapy. Adaptive therapy may be more of an academic theory than a practical way to do things. To do it well, the doctor has to have regular measurements of the tumor size and make concurrent adjustments in dosing.