UMCU

Predicting whether chemo will be effective for breast cancer

Breast cancer researchers at UMC Utrecht have discovered that a certain protein can predict whether a course of chemo will be effective for aggressive breast cancer. Women with breast cancer and a high level of FER protein have a greater chance of successful treatment with taxane chemotherapy. The results of this study were published in the renowned scientific journal Cell Reports.

Triple-negative breast cancer is an aggressive type of breast cancer. Women with triple-negative breast cancer often receive treatment with chemotherapy. The goal of the chemotherapy is to reduce the risk of metastasis (spread of the cancer) as far as possible, which increases the chances of survival.

The treatment with chemotherapy is not equally effective for all women. Many women also often suffer unpleasant side effects, such as fatigue, anemia, nausea, and hair loss. “It would be really helpful if we could predict whether a treatment with chemotherapy will be effective,” explains Patrick Derksen, professor of pre-clinical oncology at UMC Utrecht.

High FER protein, greater benefit of chemotherapy

His research group discovered that a certain protein could predict whether a course of chemo will be effective for triple-negative tumors. Women with breast cancer and high levels of the so-called “FER protein” will benefit more from treatment with chemotherapy.

Specifically, they will benefit from chemotherapy with taxanes, a type of medication that slows down cell division. “The FER protein basically recycles other proteins that the cancer cells need to be able to spread,” Derksen explains. “The taxanes slow down this process.”

Test that indicates whether chemotherapy will be beneficial

The researchers are now working on developing a test that demonstrates whether a triple-negative breast tumor has high or low levels of FER protein. High levels of FER equate to a greater probability of the taxane chemotherapy being effective.

Derksen: “We want to start using the test right from the moment of diagnosis, so that we can offer a more tailored treatment. The test is performed in the lab on collected tumor material. We do not need to ask the patients to do anything extra. We will conduct clinical trials on this test, to confirm our prediction and so be able to offer a more personalized and effective treatment.”

Further information

Source: UMCUtrecht

Project stories: interview with Thijs Koorman

Project stories: interview with Thijs Koorman

The ultimate goal of the Mechano·Control project is to be able to abrogate breast tumour progression. To do that, it is very important to apply the Mechano·Control findings at different scales, from single molecules and all the way up to the organism and patient level. For that, Thijs Koorman, a senior postdoc at the DerksenLab at the UMC Utrecht, will perform fundamental  and preclinical research within in the Mechano Control project. His main goal is to translate basic findings with therapeutic potential to target invasive breast cancer. With this interview, we are going to take a step forward and get a closer look to the animal and human models, the largest scale of the Mechano·Control consortium.

Dr. Thijs Koorman runs a variety of different tasks. But first, let’s get to know a little bit more about their role in the Mechano·Control consortium. The main aim within the DerksenLab  is to translate the molecular findings within the Mechano·Control project to animal and human models of invasive breast cancer. This group has a fundamental to translational focus. They provide proof of concept in preclinical models of breast cancer and test novel candidate targeted therapeutic interventions identified within Mechano·Control.

With this in mind, Thijs together with Dr. Daan Visser (technician within the Mechano Control consortium) test the therapeutic potential of the identified molecules in the consortium with the hope to obtain pre-clinical data that can be used to ultimately better treat patients suffering from invasive breast cancer.

And how is this translated into the lab?

“We culture mouse and human organotypic cancer models in both 2D and 3D. The models used represent the two types of invasive breast cancer. As such, they harbour all aspects of human invasive breast cancer, which we study using molecular biochemistry and microscopy”, explains Thijs.       

In particular, Thijs studies the molecular and signalling composition of cell adhesion proteins and how disruption of this complex potentiates oncogenic signalling. For this he uses 2D and 3D organotypic tumor models and preclinical mouse models of invasive breast cancer. The group has a deep interest in how loss of mechano-transducing cell-cell and cell-matrix contacts drive to invasive breast cancers, focussing on lobular carcinoma. The groups has generated a breast cancer sample database of over 2000 patients and collected tumour material of over >1000 patients to test molecular markers.

LEFT PANEL: Multiple examples of breast cancer samples, punched from human invasive breast cancers as spotted as a micro-array cores. Top two cores are H&E stainings, bottom two cores are immunohistochemistry (detection of specific proteins in tissues using antibodies). RIGHT PANEL: Triple immunofluorescence-staining image of a developing breast tumor.

Until now, Thijs and the researchers at the Derksen Lab have discovered a molecular mechanism that explains how invasive breast cancer cells may stop dividing and linger in the body for years and what triggers expansion at the metastatic site. Now, they are probing how to target these “sleeping cells” during dissemination and stop the growing cells with therapeutics.

Discovery-based fundamental science is essential to establish the building blocks of therapeutic interventions. “We aim to bridge both aspects, understanding the molecular signalling and discovering or identifying the means to target them. Most importantly, we have the tools to test such in our clinical mouse models and all subtypes of invasive breast cancer. Being able to make these translational steps fast and efficient is a unique aspect of our work” says Thijs.

Thijs also supports the day-to-day supervision of bachelor, master and the Ph.D. students. He also teaches a variety of undergraduate classes at Utrecht University. Thijs also manages the clinical outsourcing and dissemination, including patient advocate involvement. Thijs also holds a leadership position within the COST Action Lobsterpot (CA19138), an initiative of the European Lobular Breast Cancer Consortium (www.elbcc.org).

According to Thijs, being a part of the Mechano·Control consortium is a thrill and a great opportunity to work with colleagues all over the world that work at very different scales. “A single email, text or conversation is sufficient to spark new ideas or endeavours. Combining all of our skills and thinking outside the box is exciting. Not only for your own development, but also to obtain new views on scientific problems. We have a collaborative spirit and were able to test a lot of hypotheses which otherwise would not have been tested.”