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Gremke Group

Based on novel insights in tumor biology within the last years, a plethora of different molecular cancer targeted therapies (e.g. CDK4/6- and PI3Kinase-Inhibitors) have entered clinical practice and improved the therapy of HR+, HER2- and PIK3CAmut metastasized breast cancer. However, the phenotypic plasticity and inherent genomic instability allow tumors, to rapidly evolve drug resistant subclones as a cause of intrinsic or acquired therapy resistance and eventually lead to tumor relapse and therapy failure.

As a key driver of cancer drug resistance, increased mTOR signaling is associated with resistance to various targeted drugs. mTORC1 functions hereby as a central integrator of oncogenic signaling cascades and impedes the initiation of the cellular self-digestion process, named autophagy. Given the central role of autophagy in cellular energy homeostasis, activation of mTORC1 signaling suppresses autophagy and thereby deprives cells of a powerful survival mechanism to compensate metabolic perturbation induced by various compounds targeting cancer metabolism. Thus, resistant cancer cells with aberrant mTORC1 signaling activity suffer severe energy stress and induce apoptosis.

Based on these findings current research in the group is exploring the translational potential of metabolic drugs for overcoming treatment resistance in breast cancer.

Funding:
Stiftung P.E. Kempkes (01/2021)
UKGM Research Grant (03/2022 MR)
UCT Frankfurt-Marburg
SUCCESS Program of the Philipps-University Marburg