Although there are more than 100 approved drugs to treat cancer, predicting which drugs will help a particular patient remains complex. To overcome this issue, MIT researchers developed a small implantable technology that carries up to 30 small doses of different drugs. The study reporting this new device is published in the journal Science Translational Medicine. Following the implantation of this new device in a tumor allowing the drugs to diffuse into the tissue, the investigators can measure the effectiveness of each drug in killing cancer cells.
According to Oliver Jonas, paper lead author and postdoc at MIT’s Koch Institute for Integrative Cancer Research, this new device can potentially reduce much of the guesswork involved in selecting cancer treatments. “You can use it to test a patient for a range of available drugs, and pick the one that works best,” Jonas said in a recent news release.
The majority of the drugs targeting cancer damage the DNA and interfere with cell normal function. Currently, researchers have developed targeted compounds that kill tumor cells with particular genetic mutations. Nevertheless, it remains complex to determine the effectiveness of a particular drug in an individual patient.
Normally, tumor cells are extracted, grown in lab dishes, and treated with different agents in order to determine which ones are the most efficient. But as Jonas said, this method removes tumor cells from their natural environment, which can play a key role in the tumor response to drug treatment. “The approach that we thought would be good to try is to essentially put the lab into the patient,” he said in the news release. “It’s safe and you can do all of your sensitivity testing in the native microenvironment.”
The new technology is made of a crystalline polymer, and is implanted in the tumor with a biopsy needle. Following the implant, the drugs diffuse between 200 to 300 microns into the tumor, however, they do not overlap with each other. Since any drugs can go inside this device, scientists can determine the drugs dosing that will target the cancer cells, similarly to traditional intravenous injection.
The implant is removed after one day, along with a small sample of a tumor’s surrounding tissue, so researchers can evaluate the drug effectiveness by staining the tumor sample with antibodies to detect markers of cell death or spread.
In this new research, the scientists implanted the device in melanoma, breast and prostate cancer mice models, since these cancers are known to have varied sensitivities to different cancer drugs. Then the MIT researchers tested if their results corroborated those previously-seen differences.
They then examined the effectiveness of the device in triple negative breast cancer, which is a cancer that lacks Her2, a progesterone receptor, and the estrogen receptor markers. This type of breast cancer is very aggressive, since none of the drugs used against it are targeted to a specific genetic marker.
Results revealed that these tumors responded differently to five of the drugs commonly used as treatment, and that the most effective were paclitaxel, doxorubicin, cisplatin, gemcitabine, and lapatinib, respectively.
The researchers then delivered these drugs by intravenous injection. The results were the same, indicating that the device accurately predicts drug sensitivity.
In their research, they compared single drugs to each other, however, this new device can also be used to examine different combinations of drugs, according to Jonas.
“This device could help us identify the best chemotherapy agents and combinations for every tumor prior to starting systemic administration of chemotherapy, as opposed to making choices based on population-based statistics. This has been a longstanding pursuit of the oncology community and an important step toward our goal of developing precision-based cancer therapy,” said Jose Baselga, chief medical officer at Memorial Sloan Kettering Cancer Center and an author of the paper.
The MIT team will now do research on making the device easier to read while inside the patient, in order to get faster results. Next year, the team is planning to conduct a clinical research trial in patients with breast cancer. The device can also be used for the development or for the evaluation of drugs to treat cancers such as prostate cancer. Another application is the creation of different variants of an encouraging compound and assess its effectiveness in a small human patients clinical trial, in order to select the best one to carry on to a larger clinical trial.