24 April 2018

Annemarie Post and Paul Span from the new Radiotherapy & OncoImmunology lab of the department of Radiation Oncology, theme Women’s cancers, and colleagues investigated common features of tamoxifen resistance and radioresistance in breast cancer. Their findings will be published in the journal Clinical Cancer Research.

Publication: link

Treatment resistance is a main cause of adverse disease outcome in breast cancer patients. Therefore, this study aimed to identify common features of tamoxifen- and radioresistance in breast cancer cells in vitro and investigate relevant pathways in patient cohorts to establish the relevance of the identified pathways.
 
Both tamoxifen- and radioresistant breast cancer cells had increased expression levels of genes involved in type I interferon signaling, compared to non-resistant cells. IFN-stimulated genes (ISGs) were induced in a dose-dependent and time-dependent manner after tamoxifen treatment and irradiation. Tamoxifen treatment also led to ssDNA presence in the cytoplasm, a phenomenon that has already been described for irradiation and is known to induce expression of ISGs.
 
Several breast cancer patient cohorts were analyzed to investigate the relation of ISG expression with treatment sensitivity. In one cohort, high expression levels of ISGs were found in the primary tumor in around half of the patients. This was associated with a tumor infiltrating lymphocyte expression signature, while the ISGs were also expressed by the tumor cells themselves. Importantly, the expression of ISGs correlated to outcome in breast cancer patients treated with adjuvant tamoxifen or radiotherapy, but not in systemically untreated patients or chemotherapy-treated patients.
 
These data indicate that expression of ISGs by tumor cells is involved in acquired, treatment-induced resistance to tamoxifen and radiotherapy, and might play a role in intrinsic resistance via interaction with tumor infiltrating lymphocytes.

Paul Span

Related news items


Online intervention for women exposed to intimate partner violence

21 November 2019

Within the SAFE project from the department of Primary and Community Care an eHealth intervention has been developed for women exposed to intimate partner violence (IPV).

read more

A personal touch of Sander Leeuwenburgh

21 November 2019

In order to promote interaction amongst colleagues within RIMLS, we have a ‘personal touch’ series setting employees in the spotlight. A light-hearted manner to learn about the colleagues you know and those you don’t. This week: Sander Leeuwenburgh.

read more

Technology for Oncology II grant application funded

21 November 2019

The grant application called "aiREAD – Accurate and Intelligent Reading for EArlier breast cancer Detection” by project leader Ioannis Sechopoulos, has been selected for funding under the NWO TTW – KWF Kankerbestrijding – Top Sector LSH Partnership “Technology for Oncology II”.

read more

KNCV Golden Master Award call for nominations

20 November 2019

The Royal Netherlands Chemistry Society awards this prize each year to the best Master’s research project. The Master’s thesis must relate to research in the field of chemistry, life sciences, process technology or (bio-)molecular sciences. Deadline: 31-12-2019.

read more

Podosome nanoscale architecture redefined

20 November 2019

Koen van den Dries and Alessandra Cambi, theme Nanomedicine, revealed how the nanoscale architecture of podosomes enables dendritic cells to protrude and sense their extracellular environment. They have published their results in Nature Communications.

read more

270 times Homo Universalis in Nijmegen

20 November 2019

What does a scientist of the future look like? International young scientists addressed this important topic during the ENABLE conference, organized by young researchers for young researchers. They showed how the new generation of researchers wants to open up science to the public.

read more