On October 19 the World Health Organization celebrates the International Day against breast cancer with the aim of raising awareness and promoting woman´s access to timely and effective controls, diagnoses and treatments.
Several CIC biomaGUNE laboratories are conducting research on the early detection and improving breast cancer progression and treatment.
The Radiochemistry and Nuclear Imaging Group headed by Dr. Jordi Llop participates in the collaborative BREAST-BRAIN-N-BBB project lead by the University of Lisbon (funded by Fundación La Caixa) which aims develop a novel anticancer drug to treat brain metastasis derived from breast cancer.
The project aims to address the challenge of breast cancer spreading to the brain, a difficult-to-treat scenario due to the brain's protection against external molecules. The international team plans to develop a smart drug, inspired by the body's antibodies, to target and eliminate aggressive breast cancer cells in both the breast and the brain.
In collaboration with Prof. Miguel Castanho (iMM), Prof João Gonçalves (iMed) and Dr Charles Lawrie (Biogipuzkoa Health Research Institute) “we are trying to develop intelligent transporters capable of crossing the blood-brain barrier, accumulating selectively in brain metastases and releasing the active drug in a localized manner,” says Llop. “CIC biomaGUNE's contribution focuses on investigating whether the drugs reach the metastases, and then assessing the therapeutic effect in animal models,” adds.
The Bionanoplasmonics Group headed by the Ikerbasque Professor Luis Liz-Marzán and the Hybrid Biofunctional Materials Group led by the Ikerbasque Fellow Dr. Dorleta Jiménez de Aberasturi both work on the development of 3D printed breast cancer models.
The Bionanoplasmonics Group leads the 3D TUMOR project towards personalized breast cancer medicine. It aims to recreate the complexity of breast carcinomas by developing novel 3D bioprinted breast tumor models with a decellularized extracellularized matrix of breast tissue. These models will have the potential to reflect the biological complexity of the disease by reproducing multiple parameters of the tumor microenvironment. The ultimate goal of this project will be the development of 3D tumor models created from patient biopsies for pre-clinical testing of targeted therapies. These platforms will be used to test and monitor the specific therapeutic effectiveness of drugs, which will help identify the most appropriate treatment regimens for individual patients, thus moving towards personalized medicine.
In a collaborative effort with the group of Prof. Ander Izeta at IIS Biogipuzkoa, Jiménez de Aberasturi explains that they have developed three-dimensional (3D) breast tumor models to be used for drug testing in a preclinical phase.
As reported in the “3D bioprinted breast tumour-stroma models for pre-clinical drug testing” article, published in the Material Today Bio journal, by combining a mix of breast decellularized extracellular matrix and methacrylated hyaluronic acid with tumor-derived cells and non-cancerous stromal cells of biological relevance to breast cancer, they show that biological signaling pathways involved in tumor progression can be replicated in a carefully designed tumor-stroma environment. They demonstrate proof-of-concept application of these models as a reproducible platform for investigating therapeutic responses to commonly used chemotherapeutic agents.
The Hybrid Biofunctional Materials Group in collaboration with the group of Amaia Cipitria (IIS Biogipuzkoa) focuses on developing 3D Printed and Microfluidic Models of Breast Cancer lung Metastasis.
Following the brain, the lung ranks among the organs most commonly impacted by breast cancer metastasis, along with the bones and liver, and its appearance can vary greatly from one patient to another, with some women suffering metastasis up to decades after the initial diagnosis.
“We are focusing on designing 3D in vitro lung models that help to study different factors that influence metastatic cell activation, such as extracellular matrix stiffness, and see how metastatic growth of latent breast cancer cells is directly affected,” Dr. Jimenez de Aberasturi says.
The Molecular and Functional Biomarkers Group at CIC biomaGUNE headed by the Ikerbasque Professor Jesús Ruiz Cabello has established a close collaboration with the breast cancer group led by Dr. María Caffarel at IIS Biogipuzkoa to study the role of inflammation and fibrosis in breast cancer metastasis using molecular imaging.
In several cancers, including breast cancer, there's a kind of long-lasting, mild inflammation happening inside the body, and this inflammation is pretty important. Cytokines are like messengers for inflammation, and they have a big role in helping cancer spread to other parts of the body.
Peio Azcoaga, PhD student working on the INFLAMMET project, found that these cytokines mess with how cancer cells use food and talk to their surroundings. They also change the microenvironment around the tumor, making it more hostile to the anti-tumor effect of immune system cells, lacking in nutrients and with increased acidification.
The relevance of this research is that it helps us understand this specific cytokine called Oncostatin M and how it helps tumors grow in their environment. If this idea turns out to be true, we might be able to use special antibodies to block these cytokines and come up with a new way to treat advanced breast cancer.
In collaboration with the Biomolecular Nanotechnology Group at CIC biomaGUNE led by Ikerbasque Professor Aitziber L. Cortajarena, the group of Professor Jesús Ruiz-Cabello is working on improving the evolution and treatment of breast cancer through the use of multifunctional tools based on biomolecular engineering that have a combined anti-fibrotic and anti-tumor effect. In the framework of this project, protein-nanomaterial hybrids with both therapeutic and diagnostic properties, acting as theranostic agents, are being developed. These nano-tools have the capacity to act both as anti-tumor and anti-fibrotic therapy, and to monitor the evolution of the tumor and the fibrosis associated with it using in vivo Molecular Imaging techniques, such as Magnetic Resonance Imaging.
The main objective of the project is to improve the ability to diagnose and treat cancer and associated fibrosis, associated with poor response to certain treatments, more effectively. By better understanding the relationship between these two conditions, the project also seeks to explore new therapeutic options using biological drugs.
The Biomolecular Nanotechnology Group is also developing effective and efficient tools for cancer therapy using a combination of protein engineering and nanotechnology. In particular, the PROTHER project focuses on combination therapies for cancer, where engineered protein-nanomaterial hybrids will also be designed to achieve both photothermal properties as well as therapeutic catalytic effects encoded in the nanomaterial. These agents will be applied in emerging multimodal strategies that include chemotherapy, photothermia and enzymatic activities in a single therapeutic element. The protein-nanomaterial hybrid-based tools for the two proposed applications will be evaluated and validated in breast cancer models.