Improving bone health in cancer – a concept from basic research to clinical impact
Prof. Dr. med. Tilman Rachner
Maintenance of bone health remains a major challenge in cancer care. Bone metastases are frequent complications of advanced malignancies and are difficult to treat, while cancer therapies themselves often impair bone metabolism, leading to bone loss and an increased risk of fractures in cancer survivors. Yet, structured programs to support bone health in this growing group of patients are lacking, resulting in underdiagnosis and undertreatment of patients at high risk of metabolic bone disease. Moreover, bone metastases are often detected late, and no clinical biomarkers exist for their early detection.
Assessing the biological and prognostic role of dickkopf-1 (DKK1) in bone-seeking malignancies. A Kaplan-Meier survival curves of prostate cancer patients showing overall survival (OS) in relation to their dickkopf-1 (DKK-1) serum levels. B Bioluminescence imaging of mice three days after intracardiac injection of luciferase-tagged PC3 prostate cancer cells into the left ventricle. Cells were silenced with siRNA against DKK1 or non-targeting control, one day before injection.
Current research
To address these challenges, we aim to improve both our basic understanding of bone biology in cancer as well as bone metastases and to advance individualized patient care. Over the past decade, our team of basic researchers and clinician scientists has pursued translational projects to unravel the pathophysiology of bone metastases and enhance clinical management. Together with our collaboration partners, we employ a wide range of approaches including cell culture experiments with bone-seeking tumor cells, analyses of public databases, biomarker investigations using clinical samples, and tumor models in mice and zebrafish.
Our research projects comprise biomarker studies in patients with osteotropic malignancies such as breast and prostate cancer, investigations on bone health and vitamin D after stem cell transplantation, and basic research key molecular pathways such as the Wnt-inhibitor Dickkopf-1 (DKK1), the mevalonate pathway, and inflammatory axes. We are particularly interested in deciphering the complex mechanisms driving early and late stages of bone metastases, which involve a synergy of local and systemic soluble and cellular mediators. Moreover, our research addresses the impact of both osteotropic and non-osteotropic tumor growth as well as anticancer therapy, on bone health in affected patients.
Research aims
- Investigating the role of Dickkopf-1 in the context of tumor inflammation processes
- Unraveling the impact of tumor-associated inflammation on metastatic behavior
- Identifying and characterizing novel biomarkers in osteotropic and non-osteotropic tumors
- Establishing new healthcare structures to improve hormonal health in survivors of cancer
Active team
Andy Göbel, PhD │Scientific and administrative coordinator
Sophie Pählig, PhD │Postdoc │Research scientist
Dorit Breining, MSc │Research assistant
Selected publications
Link-Rachner CS, Göbel A, Jaschke NP, Rachner TD. Endocrine health in survivors of adult-onset cancer. Lancet Diabetes Endocrinol. 2024;12:350-364
Göbel A, Pählig S, Motz A, Breining D, Traikov S, Hofbauer LC, Rachner TD. Overcoming statin resistance in prostate cancer cells by targeting the 3-hydroxy-3-methylglutaryl-CoA-reductase. Biochem Biophys Res Commun. 2024;710:149841.
Jaschke NP, Breining D, Hofmann M, Pählig S, Baschant U, Oertel R, Traikov S, Grinenko T, Saettini F, Biondi A, Stylianou M, Bringmann H, Zhang C, Yoshida TM, Weidner H, Poller WC, Swirski FK, Göbel A, Hofbauer LC, Rauner M, Scheiermann C, Wang A, Rachner TD. Small-molecule CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response. Immunity. 2024;57:364-378
Göbel A, Rachner TD, Hoffmann O, Klotz DM, Kasimir-Bauer S, Kimmig R, Hofbauer LC, Bittner AK. High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. Arch Gynecol Obstet. 2024;309:2789-2798
Jaschke NP, Pählig S, Sinha A, Adolph TE, Colunga ML, Hofmann M, Wang A, Thiele S, Schwärzler J, Kleymann A, Gentzel M, Tilg H, Wielockx B, Hofbauer LC, Rauner M, Göbel A, Rachner TD. Dickkopf1 fuels inflammatory cytokine responses. Commun Biol. 2022;5:1391
Link-Rachner CS, Rachner TD. Long-term bone health in childhood cancer survivors: underappreciated and undertreated? Lancet Diabetes Endocrinol. 2023;11:2-3
Rachner TD, Coleman R, Hadji P, Hofbauer LC. Individualized Bone-Protective Management in Long-Term Cancer Survivors With Bone Metastases. J Bone Miner Res. 2021;36:1906-1913