Every drug has side effects, and the question is usually how to assess the risk of the cancer drug side effects vs. benefit of the particular medication.
But what if a stem cell test could predict how a particular patient would react to a particular drug? What if physicians knew this before starting a treatment regimen, and could swap one drug for another or alter the dosage of a drug?
“Essentially, such identification will allow clinicians to begin at lower drug doses, and to increase as needed,” says Dr. Min-Han Tan, an oncologist and principal research scientist at the Institute of Bioengineering and Nanotechnology (IBN) in Singapore.
Adverse reactions to prescription drugs send hundreds of thousands of people to emergency rooms each year, often leading to hospitalizations, and their numbers continue to rise. Why is this happening?
Because there are more drugs available to treat patients today than ever before, and people often take drug combinations for a particular ailment. Many patients also take a cocktail of drugs for multiple health issues, which increases the risk of adverse reactions.
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Potential for Screening Harsh Cancer Drugs
Tan’s team at IBN have devised a stem cell test they used to screen a kidney cancer drug to see if it will cause liver damage, and how it causes damage.
As part of a 4-year-long research project, researchers drew the blood of 5 patients, and using induced pluripotent stem (IPS) cells that can transform into different types of cells, they created liver cells which were then exposed to Votrient (pazopanib), a chemotherapy drug for late-stage kidney cancer (advanced renal cell carcinoma) that can cause liver damage.
They found that 3 patients reacted badly, while 2 had no liver damage. The stem cells that were tested mirrored the reaction that patients actually had post-treatment.
“We were able to figure out how the drug works from the [patients’ reaction] to the liver cells, which was unknown to doctors, even after many years of using this drug,” Tan says.
Pazopanib causes adverse reactions such as hepatotoxicity (liver damage), hypertension, hand and foot rash, and fatigue. Drugs that damage the liver can lead to organ damage and chronic disease.
Personalized Testing Trumps Generic Tests
The researchers pointed out that currently, new drugs are tested for toxicity using generic liver cells, which can’t model a patient’s specific reaction. By personalizing liver cells from individual patients’ blood, the stem cell test can help doctors prescribe safer and more effective therapies. The team is planning on a formal clinical trial for further testing.
“We are already working on expanding the patient cohort (test group) and targeting different types of organs, other than the liver, to evaluate drug toxicity in these organs,” Tan says. “The reliability of such testing is best determined in larger cohorts and studies, which we look forward to reporting.”
‘The whole idea of patient-specific therapies, including for cancer, is an exciting new trend’
This is a good start and looks encouraging, says Paul Knoepfler, a biomedical scientist at the University of California, Davis, who focuses on stem cell and cancer research.
“While I have not seen exactly this kind of stem cell-based test before, the big picture idea of using IPS cells for drug testing has already generated a lot of excitement, and I think has tons of promise,” Knoepfler says. “The patients’ own cells, particularly liver cells, are ideal for gaining insights on predicted patient drug reactions.”
While it’s too soon for patients to be asking for this test, if it’s scaled up and adopted by healthcare providers following clinical trials, it won’t hurt to ask he says, since he always encourages patients to ask questions.
A Combined Approach
However, physicians typically won’t rely on a single test to decide which patients should be given which drugs. Instead, they would use this test in combination with other data such as genomic testing, which could provide the best predictions.
“The whole idea of patient-specific therapies, including for cancer, is an exciting new trend, and I see this kind of stem cell technology, perhaps together with patient genomic testing, as a major step forward,” Knoepfler says.
Tan’s team is working on scaling up the test for wider adoption, so it can reliably detect and avoid side effects, which he says would be reduced by at least 90%.
But a big question is cost. Would it be an affordable test? “It’s still in the proof of concept stage, but if commercialized, we hope to make the test affordable for the average patient,” Tan said. The current process takes 6 months, but we’re working on reducing the cost and the turnaround time to take it from lab to clinic.”
