Finding safe and effective oncology treatments.

Mystery of cancer: various mechanisms and treatment targets

Cancer is defined by dysregulated gene expression and cell cycle progression that leads to uncontrolled cell proliferation, tumor growth, and metastasis. Traditional oncology drugs target DNA replication and cell proliferation, but are non-selective and have serious side effects. More recent immune-oncology approaches focus on cell cycle regulation (e.g. PD-1 checkpoint inhibitors) and using the immune system to attack cancer cells, alongside antibodies (e.g. Keytruda, Herceptin), antibody-drug conjugates (ADC) and small molecules to inhibit transcription factors, kinases, and other signaling pathways. However, recently ion channels have become a promising players in the field of oncology and a relevant target for the development of novel anticancer therapies.

Cancer as a channelopathy

Ion channels and pumps involved in cancer

Ion channels such as sodium, potassium, chloride, and calcium channels, and ion transport pumps are among the many proteins affected by aberrant gene expression in cancerous cells. Aberrant cell migration, cell adhesion, and cell cycle control all contribute to the invasive phenotype associated with metastasis, and ion channels and pumps have been reported to play a key role in these mechanisms of cancer generation (figure adapted from Litan and Langhans, Front. Cell. Neurosci., 2015).


Ion channels as therapeutic targets for cancer

Ion channels have been identified as potential therapeutic targets for cancer treatment because of their role in regulating cell growth and proliferation. By targeting specific ion channels that are overactive or overexpressed in cancer cells, it may be possible to inhibit the growth and spread of the tumor. For example, TRPV1, TRPV2, and TRPV6 channels have been studied as potential therapeutic targets in prostate cancer and potassium channel inhibitors have been shown to inhibit the growth of lung cancer cells. However, it is important to distinguish between bystander effects and causative links between ion channel activity and tumor growth. For example, the hERG1b isoform of the cardiac channel has been linked to the growth of certain cancers, and over-expression of Nav1.5 and Nav1.7 channels correlates to proliferative activity in breast and prostate cancer, inhibitors of voltage-gated calcium channels have been shown to inhibit the growth of breast and prostate cancer cells.

Recommended reading: Jiang L-H, Adinolfi E and Roger S (2021) Editorial: Ion Channel Signalling in Cancer: From Molecular Mechanisms to Therapeutics. Front. Pharmacol.


CAR T cell therapy in

treatment of cancer

Using immune response to fight cancer

Recently, the human immune response emerged as a very powerful tool for fighting cancer. The field of immuno-oncology is focused on understanding how cancer cells escape cell cycle regulation and immune system surveillance to proliferate and metastasize, and the use of immunological ligands (e.g. antibodies, cytokines), signaling pathways (e.g. checkpoint inhibition) and immune cells to attack and kill cancer cells (CAR T). Cell-based proliferation and cytotoxicity assays are a fundamental part of immune-oncology screening cascades. The use of human cancer cell assays offers better translation to the clinic, and can also study the development of oncology drug resistance, increasing the successful development of safer and more effective anti-cancer treatments. Impedance-based technology is emerging as a new, powerful tool to monitor cytotoxicity, the efficiency of various immune-oncology treatments, such as CAR T, and their effects on cancer cell proliferation.

In general, identifying T cells that kill cancer cells in vivo is critical to the development of successful cell therapies. The label-free AtlaZ immune cell killing assay can be used to measure rate of killing at Effector:Target (E:T) ratios to predict in vivo activity. In order to gain a deeper understanding of cancer cells, real-time and continuous monitoring is necessary to access kinetic and phenotypic information. Figure depicts the workflow of immune cell-mediated killing assay. Target cells are seeded in AtlaZ sensor plates, adhere to and proliferate (1), then non-adherent effector cells are added (2). The cytolysis of the target cells is measured and displayed as Cell Signal over time.

Assay platforms for immunology

and immuno-oncology

Electrophysiology and impedance applications

Automated patch clamp electrophysiology can record voltage- and ligand-gated ion channels in immune cells, discover how they regulate and respond to cell activation, and identify drugs to treat inflammatory and auto-immune diseases. Modulators and blockers of potassium channels and cation channels (e.g. Orai-Stim), such as ShK toxin Kv1.3 inhibitors, have been tested in cell lines and T-cells, on Port-a-Patch and SyncroPatch 384.

Our new AtlaZ impedance system enables label-free, continuous, real-time monitoring of cancer immune therapy effects in acute and chronic experiments that mirror in vivo treatment regimes and in high throughput (simultaneously using six 96-well plates). This approach gives researchers the necessary tools to gain deeper access to the kinetic and phenotypic cellular responses. Label-free impedance recordings from human iPSC-derived cardiomyocytes using CardioExcyte 96, are also useful in detecting chronic cardiotoxicity of chemotherapy drugs. Thus, using human cancer cell assays can enable the better translation of new compounds to the clinic and help understand the development of oncology drug resistance, increasing the successful development of safe and effective anti-cancer treatments.

How can we help you?

Contact our specialist Dr. Elena Dragicevic (Senior Sales and Alliance Manager). Elena is delighted to help you:
or call: +49 89 2190 95-081
or connect via LinkedIn