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Peter Weber

Tumor Relapse in Head and Neck show molecular Dynamics and Heterogeneity


Therapy-resistant head and neck tumors and their relapses exhibit molecular profiles that, as now discovered, indicate marked tumor heterogeneity and molecular dynamics within one patient. The composition of tumor subpopulations influenced by therapy and their molecular characteristics were recently presented by Horst Zitzelsberger, Peter Weber and other members of the Research Unit Radiation Cytogenetics (ZYTO), together with researchers from the LMU Klinikum and the former Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Tumors", and in collaboration with the University of Lübeck and the Rechts der Isar Hospital, in their joint publication in Clinical Cancer Research.

Genetic similarities between primary and recurrent tumors after radiation therapy reflect the extent of tumor heterogeneity and therapy-driven selection of tumor subpopulations. To date, molecular characteristics of therapy-resistant tumor populations have not been taken into consideration in the development of treatment regimens for recurrent tumors. This new finding, however, could represent a new, promising therapeutic approach.

Sequencing revealed sometimes-significant genetic differences between tumor pairs as well as between individual tumor cells. A change in molecular subtype in about half of the tumor pairs indicate therapy-related selection of subpopulations or molecular reprogramming. The analysis of tumor genomes showed little concordance in mutant cancer genes and revealed the presence of different tumor subpopulations within one patient. In recurrent tumors, selection predominantly favored a specific molecular subtype namely basal subtype with features of epithelial-mesenchymal transition.

"The kind of tumor heterogeneity observed within one patient suggests that the recurrent tumor's molecular profile should also be taken into consideration for therapy decisions," Zitzelsberger explained. "This is where targeted molecular therapies for subtypes could be developed." “The results additionally show that reprogramming at the transcriptome level plays a much more important role than genomic mutation analysis, which has been the standard approach in tumor boards," added Peter Weber, one of the lead authors of the publication.