Live Cell-Based Drug Screening Helps Bring Personalized Medicine to Cancer Patients

Personalized medicine , which tailors treatments to individuals based on their unique characteristics, has emerged as a promising way to tackle cancer. Learn how one group is leveraging live cell-based screening to match pediatric cancer patients with better treatments.

^{This article is posted on our Science Snippets Blog}  

Cancer is a complex disease that affects millions of people worldwide. While traditional treatments such as chemotherapy and radiation therapy have been effective in many cases, they often come with bad side effects and may not even work for all patients.
Cell-based assays, which use living cells to test the effectiveness of drugs, are a key tool in this approach. By analyzing the behavior of cancer cells in response to different drugs, researchers can help reduce the risk of side effects and improve patient outcomes.

Our own Simon Bennett, Regional Business Manager at Sartorius, recently spoke with Dr. Nan Qin, Medical Faculty at the Department of Pediatric Oncology, Hematology, and Clinical Immunology Department in University Hospital Düsseldorf, about using advanced cell-based screening on late-stage anticancer drugs to get a more complete drug response profiles in their clinical studies. Here is part of the interview (link to full interview at the end).

Question: Could you describe your role and research focus?

“I am currently conducting research on group 3 medulloblastoma, which is the most prevalent malignant brain tumor found in children. This particular type of tumor has a significantly poorer prognosis than other pediatric tumors, with approximately 50% of patients succumbing to it within five years. As a result, our team has taken the initiative to construct a high-throughput drug screening process to guide personalized medicine strategies for patients.

Initially, we followed the standard procedure by incubating patient cells with drugs in a white-bottom plate for 72 hours and conducting various endpoint readouts. However, we were not able to monitor the cells throughout the process, leaving us uncertain about their condition right after dispensing into the wells, and their behavior during incubation. As a result, we encountered several  outcomes that we couldn't understand. Hence, we became intrigued by live-cell imaging and discovered that the Incucyte^® system  was a better fit for exploring drug screening for personalized medicine.”

Question: What were the major limitations with your previous workflows for culture preparation?

“In standard experiments, repeating a test is a viable option when there are doubts about the result. However, this is not possible with patient samples since there may only be a limited amount available, and only one opportunity to conduct the experiment. This means that when the data collected is of poor quality, it cannot be used to determine the appropriate treatment strategy for the patient.

By incorporating Incucyte^® into our workflow, we can gather more in-depth information about cells. Unlike before, we can now run experiments for up to 120 hours. We can monitor exactly what happens in each well from the moment we dispense the cells until we calculate the numbers. The imaging data is more accurate and reliable, giving us greater confidence in our findings. Additionally, unlike endpoint experiments, with the live-cell imaging system we no longer need to add a readout reagent that can kill cells. This allows us to conduct further experiments once we complete detection using Incucyte.

Furthermore, we can use a combination of dyes, such as Cytotox dyes and Annexin V, to get more information from each well. In some cases, the staining data can validate one another. For instance, if we notice a reduction in cell number and an increase in annexin staining, which is an indication of apoptosis, we can have more confidence in the results we obtain.”

Question: How does the Incucyte^® enable your high-throughput drug screening workflow?

“We use the Incucyte^® system to conduct two types of experiments. In our high-throughput studies, we test single concentrations of compounds and observe their response over time. For instance, we expose cells to 2.5 microliters of a drug and analyze how it affects them as time passes. Once we identify potential drugs, we subject them to dose-response testing over time.”

Question: What sort of mechanistic insights have you gained from these sets of experiments about the action of the drugs?

“Initially, we expected certain compounds to have a significant anti-cancer effect after 72 hours, but we were surprised to see no effect at all. However, after using the Incucyte^® system, we noticed that these compounds took 120 hours to start working. This observation is consistent with what we have seen in patients, where chemotherapy treatments often take several months to show results.

The Incucyte^® experiment helped us realize that we had underestimated the therapeutic effect of some compounds due to inadequate incubation time. By using live-cell imaging, we were able to better understand the dynamic drug response and optimize appropriate drug doses.”

To read the rest of this interesting conversation check out the full interview, where Dr. Qin explains the unique way they culture brain organoid models for drug testing.