Tailoring the tools to study prostate cancer metastasis

La Manna, F. (2021)

Doctoral Thesis

The work included in this thesis is aimed at developing novel tools to advance our understanding of prostate cancer. The clinical problem of prostate cancer is presented and discussed in the wider context of the current clinical knowledge, highlighting the genetic mechanisms at its base. A dedicated chapter focuses on bone metastases, highly morbid feature of advanced prostate cancer, discussing the known mechanisms and the available models to study it in translational research. Then, moving from the molecular analysis of clinical specimens of bone metastasis, a biochemical pathway is identified and further studied in vitro, ex vivo and in vivo, validating the initial findings. A novel, early-stage prostate cancer patient-derived xenograft is presented and extensively characterized and implemented in a drug screening. This allowed to screen the effect of over 70 known drugs on prostate cancer models, using three-dimensional cultures and a semi-automated platform. As all research builds on previously established findings, a bibliometric analysis tool is presented, to assist in the generation of a knowledge network arranged by topic and impact of research. All these aspects and findings are then discussed in the context of the current direction of prostate cancer research, its emerging tools and its long-known challenges.

• Patient-derived xenograft
• Organoids
• Prostate cancer
• Drug screening
• Bone metastasis
• Bibliometric analysis

• All authors: La Manna, F.
• Supervisor: Pelger, R.C.M.
• Co-supervisor: Kruithof-de Julio, M.
• Committee: Cohen, A.; Osanto, S.; Snaar-Jagalska, B.E.; Danen, E.H.J.; Kloen, P.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2021-10-14
• ISBN (print): 9789464234152