Takeda Oncology Research Award 2023 to Ann-Kathrin Daum
In some patients with non-small cell lung cancer, tumor cells carry a mutation that accelerates cancer growth. Although there are drugs that prevent this, the tumors often develop resistance to these treatments. Ann-Kathrin Daum has shown that fibroblasts of the tumor microenvironment boost the lipid metabolism of the cancer cells and contribute to the development of therapy resistance. The result could be an approach for the development of new treatment strategies.
Ann-Kathrin Daum conducts research at the German Cancer Research Center (DKFZ) and the National Center for Tumor Diseases (NCT) Heidelberg and is a junior researcher at the German Center for Lung Research (DZL). For her results, she was awarded the 2nd prize of the Takeda Oncology Award 2023.
Ann-Kathrin Daum
© Massimo Del Prete
Non-small cell lung carcinomas account for about 75 percent of all cases of lung cancer. This form of lung cancer generally grows more slowly than small cell lung cancer and therefore, in principle, has a better prognosis. However, in about six percent of the cases, the cancer cells have a mutation in the ALK gene: This gene mutation causes the enzyme anaplastic lymphoma kinase (ALK) to be overactive in the cancer cells, thereby accelerating tumor growth.
Patients with non-small cell lung cancer carrying an ALK mutation are therefore treated with so-called tyrosine kinase (TKI) inhibitors, which block the activity of ALK. However, tumor cells often develop resistance to the drug. In addition to mutation-related resistance, there is increasing evidence that influences of the tumor microenvironment may also affect the response to the ALK inhibitors.
Ann-Kathrin Daum has now been able to confirm this experimentally as part of the DZL-funded research program together with partners at the Thoraxklinik Heidelberg. She used microtumors that grew from ALK-mutated cancer cells into three-dimensional cell aggregates in the culture dish. The microtumors were cultured in the presence of cancer associated fibroblasts (CAF) and treated with ALK inhibitors. CAFs represent the major component of cells in the tumor microenvironment in many types of cancer.
Indeed, the presence of CAFs conferred resistance to various ALK inhibitors in ALK-mutated minitumors. The cancer cells died less frequently from programmed cell death apoptosis and had an accelerated cell cycle.
Using single-cell mRNA analyses, Ann-Kathrin Daum found that CAFs affected tumor cell gene activity and boosted cancer cell lipid metabolism. However, resistance development could be prevented when inhibition of ALK was combined with agents that block a key transcription factor involved in lipid metabolism."This may be an approach worth pursuing to better prevent treatment resistance in ALK-mutated non-small cell lung cancer in the future," she said.
To encourage outstanding research in the field of non-small cell lung cancer, the company Takeda Oncology has announced a high-profile research award.Ann-Kathrin Daum's project was awarded second prize, worth 10,000 euros.
Ann-Kathrin Daum studied at the Ruhr University Bochum and the Friedrich Schiller University Jena.From 2017 to 2021, she completed her doctorate at the German Cancer Research Center in the Department of Cancer Genome Research, where she has been conducting research as a PostDoc since completing her doctorate.
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.
