Interview with Dr. Åžerife Yerlikaya on exploring new horizons in cancer & ion channel research
Dr. Şerife Yerlikaya, an assistant professor from Istanbul Medipol University, spent time in Sophion’s Copenhagen labs after being awarded a research grant to investigate the effects of platinum-based chemotherapy drugs on Nav1.7 sodium currents. Working with Dr. Kim Boddum, her research grant focused on using Sophion’s advanced automated patch clamp (APC) technology to deepen our understanding of sodium channels in cancer and develop new therapeutic strategies.
After completing her work in Copenhagen, Dr. Yerlikaya discussed her achievements, including unexpected insights gained through using the Qube automated patch clamp system. Her findings highlighted the effects of chemotherapy drugs on Nav1.7 currents across different cancer cell lines, enabling the design of potential combinatorial therapies with sodium channel blockers. These results offer promising strategies to address neurotoxicity and metastasis in cancer patients, potentially transforming therapeutic approaches. Read her insights and reflections on the research grant and time working with Dr. Kim Boddum in our Copenhagen lab:
How did the results of your study align with your original aims regarding the effects of platinum-based chemotherapy drugs on Nav1.7 sodium currents?
First of all, as indicated in our previous interview, the most important goal of the project was to develop new and immediate treatment strategies for cancer patients. To achieve this, we aimed to accelerate the analysis of Nav1.7 sodium currents in metastatic cancer cell lines using the Qube automated patch clamp. Beyond our expectations, we were able to observe the effects of the drugs at various concentrations on Nav1.7 sodium currents in different cancer cell lines. These results were obtained through cumulative experiments using different types of protocols, including transient, persistent, ramp protocols, and steady-state inactivation and activation. These protocols quantitatively demonstrated alterations in Nav1.7 currents in cancer cell lines exposed to various drug concentrations.
Were there any new insights or unexpected findings from the experiments conducted using Sophion’s Qube automated patch clamp?
We carried out a protocol with the Qube that allowed us to perform more experiments with varying drug concentrations and different types of cell lines. This success was largely due to the high-throughput capabilities of the Qube system, which saved significant time and enabled the use of many more protocols for analyzing Nav1.7 sodium currents in cancer cells. As a result, we obtained more promising outcomes than expected. Based on our hypothesis that chemotherapy drugs either increase or decrease sodium currents, we established a ‘roadmap’ to analyze the effects of drug combinations (including sodium channel blockers) on the metastatic potential of cancer cells.
How do you see these findings impacting the broader field of sodium channel research in cancer treatment?
As mentioned before, Nav1.7 channels are associated not only with metastasis but also with pain. According to reported neurological effects, the negative impacts of chemotherapy could be linked to ion channel activity. Accumulating evidence suggests that various anticancer chemotherapy drugs alter the activity of voltage-gated sodium channels. Previous studies have shown that oxaliplatin and paclitaxel increase the peak currents of sodium channels in DRG neuron cells, while paclitaxel decreases the peak currents in cardiomyocytes. Along with our findings, studies of chemotherapy drugs on sodium channels could help explain both the ‘neurotoxicity’ and ‘metastatic activity’ seen in cancer patients. Additionally, future research may explore the effects of other sodium channel subtypes (e.g., Nav1.1, Nav1.3, Nav1.5, Nav1.6, Nav1.9) on pain and metastasis by broadening the expression profile across various cell types.
Considering the results, are there new directions or hypotheses you are interested in pursuing within the realm of ion channel research?
Considering our results and their effects on sodium channels, we are now exploring the activity of Nav1.7 currents in drug-resistant cells. This could lead to the development of combinatorial therapies aimed at overcoming drug resistance and mitigating neurotoxicity in cancer patients.
What do you envision as the next steps in translating these findings into potential therapeutic strategies for cancer patients?
Using the outlined protocol, we have accelerated electrophysiological studies of various drugs at different concentrations in metastatic cancer types using the Qube system. This has enabled us to plan subsequent laboratory studies focusing on cell behavior. In turn, this approach will facilitate the translation of drug-repurposing research from laboratory studies to clinical applications in a shorter time frame. Based on our findings, we plan to investigate the effects of selective transient or persistent sodium channel blockers combined with lower, non-toxic concentrations of chemotherapy drugs on metastasis.
Dr. Yerlikaya’s research showcases the critical role of automated technologies in advancing ion channel research and improving cancer treatments, with significant implications for future drug development and patient care.
Learn more about Dr. Şerife Yerlikaya’s work on sodium channels & cancer: