In most patients with ALK-positive lung cancer, modern targeted therapies initially work very well. ALK inhibitors specifically block the altered ALK protein, and the disease can often be controlled effectively for months or even years.
Unfortunately, clinical experience shows that this effectiveness does not last permanently for most patients. Over time, tumor cells learn to evade the therapy, and the cancer begins to grow again. This so-called treatment failure represents one of the greatest challenges in the treatment of ALK-positive lung cancer.
The central aim of this research project is to better understand why tumors become resistant and how this knowledge can be used to develop new and more effective combination therapies, particularly involving immunotherapies.
One focus of the project is the question of why immunotherapies work in some patients — while also improving our understanding of why this is not the case in others.
Immune checkpoint inhibitors have revolutionized the treatment of many cancers, yet only a small number of patients with ALK-positive lung cancer have shown long-term responses so far.
An important aspect is that tumors are not uniform cell populations. Even within a single tumor, different cancer cells can exist that differ genetically and biologically from one another. This diversity may contribute to some tumor cells surviving therapy and later causing recurrence of the disease.
Therefore, we specifically investigate the so-called tumor microenvironment, meaning the immediate surroundings of the cancer cells. This includes various immune cells, connective tissue cells, and signaling molecules that determine whether the immune system can attack the tumor or whether it is suppressed.
Previous studies show that some tumors have a “hot” tumor microenvironment: they contain many active immune cells and often respond well to immune checkpoint inhibitors. Other tumors are rather “cold.” They suppress the immune system and respond significantly worse to immunotherapies. Initial evidence suggests that ALK-positive tumors particularly often belong to this cold type.
Using state-of-the-art technologies, we analyze:
- which cell types are present in the tumor,
- where exactly these cells are located,
- and which genes and proteins are active within them.
The goal is to identify biological signatures (so-called biomarkers) that can predict who will benefit from immunotherapy and who will not.
Based on this, we aim to test new combination therapies in preclinical models, for example combining ALK inhibitors with immunotherapies or other targeted drugs. In the long term, this project is intended to help identify resistance mechanisms earlier, tailor therapies more individually to each patient,
and develop new treatment strategies that delay or prevent recurrence of the disease.
For the implementation of the project, access to biopsies from patients with lung cancer and an ALK translocation is essential. We are looking for patients with the diagnosis “ALK-positive non-small cell lung cancer” who fit one of the following descriptions:
Group A (Immunotherapy as first-line treatment): Patients who received immunotherapy as their very first treatment. This therapy is either still effective at present or worked well for a certain period of time.
Group B (Switch to immunotherapy after TKI): Patients who were first treated with targeted therapy (tablets such as Alectinib, Brigatinib, or Lorlatinib). After failure of this therapy or therapies, treatment was successfully switched to immunotherapy.
In addition, we would also like to gain further insights into why some tumors respond to a tyrosine kinase inhibitor (TKI) for a very long time, while others respond only briefly. Therefore, we also ask the following patients for support:
Group C: Patients who received an ALK TKI after diagnosis and continue to show a durable response.
Group D: Patients whose disease progressed after only a short time during treatment with a tyrosine kinase inhibitor (TKI).
What is required for the study?
For the analysis, we need access to the following material:
- The tissue sample from the initial diagnosis.
- Additionally, if available: the tissue sample obtained after disease progression.
Important for you: We work with so-called FFPE samples (formalin-fixed paraffin-embedded tissue). These samples are already stored in the archives of the pathology department where your biopsies were performed.
What is the process?
After contacting the research team at the University Hospital Cologne, you do not need to take care of anything else.
We do not require the entire tissue sample, only a small part of it. After the sample for our research has been taken, the remaining tissue sample will be returned to your treating hospital. The logistical process and coordination with the responsible pathology department at your hospital will be handled directly by the research team at the University Hospital Cologne.
Your contribution to research
Your participation can help generate crucial insights for the future of personalized medicine and contribute to the development of more effective treatment strategies for ALK-positive lung cancer.
Would you like to support the project with your existing tissue samples, or do you have questions?
Patients from all across Europe can contact the research team directly:
Eva Steinbach-Knödgen, University Hospital Cologne
eva.steinbach-knoedgen@uk-koeln.de
