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Individualized treatment of rare lung cancer: new insights into molecular risk factor and tumor microenvironment

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DZL scientists at the Hospital for Thoracic Diseases at Heidelberg University Hospital (UKHD) and the National Center for Tumor Diseases (NCT) Heidelberg have been working with an interdisciplinary team to investigate how a rare form of lung cancer can be better treated in an individual basis. The basis for this is identifying a molecular risk factor and deciphering the role of the immunological tumor microenvironment.

Very rare and often resistant

Among non-small cell lung carcinomas, the EGFR exon 20 mutation is very rare, accounting for about one to two percent of all cases. EGFR stands for Epidermal Growth Factor Receptor; exon 20 refers to a specific gene region where a piece of the gene is inserted. The rare tumors driven by this gene alteration are resistant to previously approved drugs and have a median survival prognosis of 18 months for those affected. The fact that tumors with the exon 20 mutation are so rare makes searching for therapeutic advances even more difficult.

Often, diagnosis is only possible through the latest sequencing methods. Twelve leading thoracic oncology centers have now used such methods in Germany-wide cooperation. They aim to identify customized and more effective treatment options for patients with rare mutations. With interdisciplinary expertise in the clinic, molecular pathology, and bioinformatics - networked in the DZL - 118 patients could be comprehensively characterized.

The molecular analysis creates the basis for treatment progress

The team recently published the study's results in the European Journal of Cancer. According to the paper, the researchers have gained important insights with genetic and transcriptomic analyses, coupled with clinical knowledge. They succeeded in identifying concurrent TP53 mutations as a new molecular risk factor and in unraveling the role of the immunological tumor microenvironment for patient survival.

Priv.-Doz. Dr. Petros Christopoulos, the Scientific Coordinator in the Department of Oncology at the Hospital for Thoracic Diseases at the UKHD and NCT Heidelberg, led the study and is the first publication author. He comments, "The interaction of genetic tumor characteristics with the immune system is the focus of our research because it is the key to healing."

Prof. Dr. Albrecht Stenzinger, head of the Centre for Molecular Pathology at the University of Heidelberg, where most of the tissue examinations were carried out, explains: "The comprehensive and integrated analysis of molecular and clinical data from patients with lung cancer creates the prerequisite for an improved understanding of tumor biology and further therapeutic advances." In addition to personalized treatment strategies, the in-depth analyses can be a first step in making changes to the design of future clinical trials. They also provide a blueprint for improved model systems in basic research.

Prof. Dr. Michael Thomas, Head of the Department of Oncology at the Hospital for Thoracic Diseases at the UKHD and the NCT Heidelberg, is the final author of the paper. He summarizes: "These results show how important successful interdisciplinary, cross-center national collaboration is to better identify tumor disease targets. The DZL plays an important role in this."

Further information:

Source: Press release of the National Center for Tumor Diseases (NCT) Heidelberg

Publication: Christopoulos P, Kluck K, Kirchner M, Lüders H, Roeper J, Falkenstern-Ge RF, Szewczyk M, Sticht F, Saalfeld FC, Wesseler C, Hackanson B, Dintner S, Faehling M, Kuon J, Janning M, Kauffmann-Guerrero D, Kazdal D, Kurz S, Eichhorn F, Bozorgmehr F, Shah R, Tufman A, Wermke M, Loges S, Brueckl WM, Schulz C, Misch D, Frost N, Kollmeier J, Reck M, Griesinger F, Grohé C, Hong JL, Lin HM, Budczies J, Stenzinger A, Thomas. The impact of TP53 co-mutations and immunologic microenvironment on outcome of lung cancer with EGFR exon 20 insertions. European Journal of Cancer. In press; doi: 10.1016/j.ejca.2022.04.020.

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