Advances in prostate cancer therapies through integrative multi-omics
Simon Linder defended his thesis at the Department of Biomedical Engineering on June 30th.
Prostate cancer is the second most common cancer in men and a frequent cause of cancer-related death. In general, prostate cancer is considered a hormone-dependent cancer, as the development and progression of these tumors are highly dependent on the action of male sex hormones called androgens. For his PhD thesis, Simon Linder researched hormonal signaling in prostate cancer and the mechanisms that lead to resistance to hormone therapy. His goal is to improve our current understanding and gain new insights to treat prostate cancer, even the ones with resistance to hormone therapy, more effectively.
Androgens can activate their direct target receptor, the androgen receptor (AR). AR is a transcription factor that plays a key role in prostate cancer, as it regulates the expression of numerous genes involved in various biological signaling pathways, ultimately leading to the growth and survival of prostate cancer cells. Given the importance of this signaling axis, several therapeutic strategies have been developed over the years to effectively block the activity of this hormone-driven regulatory pathway.
Despite these recent advances, hormone therapy inevitably leads to treatment resistance and the available therapeutic options - especially in advanced disease - remain very limited. Therefore, the identification of new targets for the treatment of therapy-resistant prostate cancer is of paramount importance to increase the survival rates of these patients.
Hormone therapy resistance
For his research, Linder therefore focused on improving our current understanding of hormonal signaling in prostate cancer and gaining new insights into the cellular adaptive mechanisms that lead to acquired hormone therapy resistance. In particular, this involved the use of so-called "multi-omics" approaches, which allow gaining precise insights into the connectivity between different signaling pathways in prostate cancer cells through collective analyses of different macromolecules (DNA, RNA, proteins). These analyses allowed us to identify previously unknown dependencies and vulnerabilities of prostate cancer whose therapeutic manipulation has the potential to improve the efficacy of currently used therapies.
This clearly demonstrates how the integration of multiple streams of data can contribute to new insights into the biology of prostate cancer, which ultimately brings Linder's goal of not only better understanding but also curing this deadly disease one giant step closer.
"It's about time!", concludes Linder.
Title of PhD thesis: "Advancing prostate cancer therapies through integrative multi-omics"
Supervisors: Wilbert Zwart and Andries Bergman (KNI)