Holding the balance; the equilibrium between ERα-activation, epigenetic alterations and chromatin integrity

Flach, K.D. (2018)

Doctoral Thesis

In this thesis we reflect on the effects differential DNA binding of the estrogen receptor α (ERα) can have on the behavior of breast cancer and which factors can contribute to this. ERα is a transcription factor than can drive tumor cell proliferation and approximately 70% off all breast tumors is thought to be dependent on the activity of this hormone-mediated transcription factor. After stimulation of ERα a wild variety of co-factors are recruited, leading to the assembly of a transcriptional complex. Although there are multiple ways of targeting the action of ERα and thereby inhibiting tumor growth, still a significant proportion of patients develop a recurrence. Cross-resistance between the different endocrine therapy options can occur, but a proportion of patients that relapse on one type of therapy can still benefit from a different treatment modality, illustrating the existence of multiple resistance mechanisms which can be treatment selective. A better understanding of ERα-biology and the development of endocrine therapy resistance, can lead the way to the discovery of novel biomarkers and potential drug targets, that can further increase patient survival.

• Cancer
• Estrogen receptor
• Breast cancer
• Genomics
• ChIP-seq
• epigenetics

• All authors: Flach, K.D.
• Supervisor: Neefjes, J.J.C.
• Co-supervisor: Zwart, W.T.
• Committee: Smit, V.T.H.B.M.; Ovaa, H.; Water, B. van de; Diest, P.J. van; Jonkers, J.; Linn, S.C.; Bergman, A.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2018-09-25
• ISBN (print): 9789463750387