A kinder, more personal cancer treatment

Two new devices promise to improve responses to chemotherapy. Viviane Richter reports. 

Oliver Jonas' device (left) is implanted in the tumour where loaded drugs diffuse into the tissue. Presage Bioscience's CIVO device (right) directly injects microdoses into the tumour tissue. – SCIENCE TRANSLATIONAL MEDICINE

Anti-cancer chemotherapy drugs are notoriously hit-or-miss. A drug that wipes out a cancer in one patient can be ineffective in another. Now two new technologies could give doctors a rapid and precise measure of a cancer drug’s effectiveness before it is pumped through a patient’s body. Oliver Jonas and colleagues at the Massachusetts Institute of Technology and Richard Klinghoffer’s team at US company Presage Biosciences published their breakthrough therapies in Science Translational Medicine in April.

“It’s taking the hydrogen bomb approach we’ve had in chemotherapy over past years and turning it into guided missiles,” says Nial Wheate, pharmaceutics lecturer at the University of Sydney.

At present, doctors can sometimes identify the best cancer treatment for a patient by decoding their tumour’s genetic signature. For example, analysing breast cancer cells from a biopsy can tell doctors if the cells carry the protein HER2 on their surface, which are vulnerable to the drug Herceptin. But doctors don’t know all the genetic signatures that indicate whether a cancer will respond to a particular drug. “There is an emerging understanding that genomics will not give us the whole picture,” Jonas says.

“It’s been a dream of mine since I started in science to do something like this for patients”

And so cancer therapy often comes down to trial and error. If one chemotherapy treatment doesn’t work for a cancer patient, doctors try another. The longer it takes to find a drug that works, the lower a patient’s chance of survival. In addition, ineffective drugs can still cause horrible side effects.

In the past, researchers tried removing cancer cells from patients, growing them in a petri dish and testing different drugs on them. But in practice the results were rarely helpful to patients. Cells grow differently in an artificial environment, so respond differently to the original tumour.

Now, the two US research teams independently answered the same question: how can we quickly test multiple drugs on tumours while they’re still inside the body?

Jonas and his team engineered a small plastic cylinder, around a tenth the size of AAA battery, with 16 small reservoirs cut into its surface that can each be loaded with a different cancer drug. The cylinder was implanted into prostate, breast and melanoma tumours in mice. The drugs leached into the tumour and after 24 hours the capsule was removed, along with half a millimetre of surrounding tissue.

Presage’s device – called CIVO – is an external handheld super-syringe equipped with up to eight needles, which each injected a small dose of a different cancer drug into a tumour under the skin. After 24 hours, the whole tumour was removed and analysed.

Each team examined the extracted tissue to see which drug most effectively killed the tumour cells around it.

Microscopy image of the fluorescent anticancer drug sunitinib gradually diffusing out of Jonas' implant reservoirs into the cancer tissue over four hours (red), 14 hours (green) and 44 hours (blue). – Oliver Jonas, Massachusetts Institute of Technology

Their results were striking.

Jonas’s implanted device ranked the performance of five different drugs. When these drug were then separately injected into the bloodstream of mice with tumours, each drug’s cancer-killing efficacy perfectly correlated with the implant’s predictions. The device even predicted which drug would best treat a “triple negative” breast tumour – a cancer type usually treated by one of five drugs but for which doctors have no genetic markers to guide treatment. “It’s been a dream of mine since I started in science to do something like this for patients,” says Jonas. The team is now preparing for clinical trials.

The Presage team also predicted which drug would successfully kill lymphoma cancer cells in mice. But their device is already further down the development line. The team successfully used it to find the best drug for human patients suffering from lymphoma, with reports of only mild discomfort and no inflammation to the injection site.

At the moment CIVO can only inject drugs to tumours near the skin. If the device makes it through clinical trials, Presage will design models to deliver the payload to deeper tumours, Klinghoffer says.

There’s no telling which technology will make it to patients first. Wheate sees Jonas’ implantable device as more “patient-friendly”. Peter Gibbs, cancer clinician scientist at the Walter and Eliza Hall Institute of Medical Research in Melbourne, says he is optimistic about both.

Because the devices are diagnostic tools, their path to the clinic is much shorter and easier than for a new cancer drug itself. If the technologies prove themselves in further clinical trials, Gibbs estimates they could be in doctors’ hands within five to 10 years. “It’s definitely exciting,” Wheate adds. “The future is personalised medicine and this is a massive step forward.”

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