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Challenges in breast cancer treatment: understanding the actions and effectiveness of anti-ER drugs

Challenges in breast cancer treatment: understanding the actions and effectiveness of anti-ER drugs

Antoni Hurtado

Universidad de Barcelona, Spain

Date: 04/03/2021
Time: 12:30
on-line
Host: Xosé R. Bustelo

Breast cancer is a heterogeneous disease and gene expression profiling has classified the tumors into several intrinsic subtypes with distinct prognostic significance. Luminal subtypes are the most frequent (around 70%) and they express Estrogen Receptor alpha (ER). ER is an estrogen activated nuclear receptor that induces a transcriptional program, which culminates in proliferation. Treatment with anti-ER therapies inhibits its function, reduces tumor growth and improves survival. One of the most successful treatments is Tamoxifen, which antagonizes estrogen effects by competing with estrogen for the binding of ER. The anti-estrogen treatments are effective in clinical practice. However, a major clinical limitation is the development of resistance to these therapies. In past years a large body of work has focused on trying to understand the underlying mechanisms leading to resistance and approaches for their circumvention. One major conclusion from these studies has been the realization that resistance is both highly complex and heterogeneous and it is clear that more work is needed to identify and improve clinical outcome of patients with ER-positive breast cancers. In my talk I will provide a revision of how anti-breast cancer drugs prevents tumor growth and I will describe novel mechanisms of action and its resistance. To obtain that knowledge we have used chemical systems approaches and combination of targeted proteomics, drug screenings, highthroutput sequencing of chromatin and sequencing of de novo transcripts (by means of GRO-seq)