Launch of a pioneering translational research programme in Europe

One of the most complex challenges in international biomedical research is how to transfer the knowledge generated in research centres to clinical practice, and vice versa, in the most efficient and timely manner possible. This process, known as translational research, has been tackled worldwide through various approaches, including placing fundamental research centres in hospitals to encourage collaboration between the two settings and the development of joint projects.

The innovative project proposed by IRB Barcelona within the framework of the pilot TRIP programme (Translational Research Innovation Programme) aims to promote research groups led by at least one scientist devoted to fundamental science and a physician who combines research with clinical practice. The TRIP project has been boosted with the support of “la Caixa” Foundation and the Dept. of Health of the Government of Catalonia.

In this first call, “la Caixa” Foundation has provided €1.2 M of funding over three years to kick-start out of the three laboratories. The first laboratory is formed by Dr. Roger Gomis (IRB Barcelona), together with Drs. Aleix Prat, Laura Angelats and Sonia Guedan (IDIBAPS), while the second is formed by Dr. Salvador Aznar Benitah (IRB Barcelona) and Drs. Cristina Saura and Isabel Pimentel (Vall d'Hebron Institute of Oncology (VHIO)). The Department of Health of the Government of Catalonia subsidises the part of the TRIP clinics sub programme that has allowed the creation of the laboratory comprising Dr. Cristina Mayor-Ruiz (IRB Barcelona) and Dr. Cesar Serrano (VHIO).

"This project will allow us to accelerate the translation of fundamental research to clinical practice, enabling it to have an impact on society sooner. Bringing together fundamental research and clinical groups in a single space to address complex diseases, such as cancer, is a paradigm shift compared to what was done until now," explained Dr. Francesc Posas, director of IRB Barcelona.

TRIP is divided into two main lines. On one hand, the TRIP - Clinics sub-programme is based on defining joint research projects between scientists at IRB Barcelona and physician-scientists at hospitals in Catalonia. This formula promotes fundamental and clinical research in the same environment, thereby facilitating collaborative access to knowledge, technological resources, and applicability. TRIP is the first project of its kind in Spain and a pioneering initiative in Europe. This integration is expected to lead to the development of new diagnostic or therapeutic tools, or the improvement of existing ones, potentially leading to new patents, the establishment of biotechnological companies, or product licensing.

On the other hand, the second line of TRIP involves the incorporation of junior group leaders to start new laboratories focused on emerging strategic fields (TRIP - Preclinical sub-programme). The junior group leaders are selected by an international committee. Researchers who have recently opened a laboratory at IRB Barcelona within TRIP include Dr. Stefanie Wculek, who heads a laboratory devoted to immunology and supported by €900,000 from “la Caixa” Foundation; Dr. Direna Alonso-Curbelo, who focuses on inflammation and its relation to cancer and ageing; and Dr. Alejo Rodriguez-Fraticelli, whose research centres on epigenomics and cell lineage tracing.

These fields are considered priority and could be defined as research opportunity niches.

INFORMATION ABOUT THE THREE TRIP-CLINICS LABORATORIES

Focus: Metastatic breast cancer
Breast cancer can be deadly if it spreads to other organs, especially when associated with drug resistance. Surprisingly, most metastases to distant organs are not caused by cells from the primary tumour but go through a prior stage in the bone, where they acquire treatment resistance before spreading. The laboratory co-directed by ICREA researcher Dr. Roger Gomis, head of the Cancer Growth and Metastasis Control laboratory at IRB Barcelona, along with Drs. Aleix Prat, Laura Angelats and Sonia Guedan, at IDIBAPS, will seek to clarify this process, which cannot be fully explained by changes in the DNA of metastatic tumour cells but requires a more dynamic adaptation to their changing environments.

Our goal is to define and understand this previously underestimated plasticity of breast cancer cells at the molecular level. Why and how does resistance to standard treatment allow breast cancer tumour cells to spread to other organs? We believe that by identifying the basis of adaptive multi-organ dissemination, we can prevent or reverse terminal breast cancer metastasis," explains Dr. Gomis. The researchers will use genetic engineering techniques to modify patients' immune cells to enable them to recognise and eliminate drug-resistant breast cancer cells. This type of therapy, known as CAR-T, has revolutionised the treatment of hematologic cancer. The project aims to translate the power of CAR-T therapy to breast cancer treatment, providing a novel therapeutic option for patients with incurable breast cancer.

Focus: A new approach for treating gastrointestinal tract sarcomas

Many types of tumours are characterised by the abnormal functioning of cell membrane proteins (Receptor Tyrosine Kinases or RTKs). Treatments for these types of cancers often rely on RTK inhibitors. While these provide significant short-term clinical benefits, most patients develop resistance in the medium to long term. In response to this clinical need, Dr. Cristina Mayor-Ruiz, head of the Targeted Protein Degradation and Drug Discovery laboratory at IRB Barcelona, and Dr. César Serrano, head of the Sarcoma Translational Research Group at VHIO, have launched a project to find alternative therapies. They are initially focusing on gastrointestinal tract sarcomas.

Targeted protein degradation is a novel pharmacological strategy that leverages the cellular process of specifically marking undesirable or non-functional proteins for destruction in the protein-shredding complex called the proteasome. The research team will explore the potential of degrader drugs to induce the elimination of relevant proteins as a therapeutic target against gastrointestinal sarcomas.

Targeted protein degradation provides an alternative to attack these RTK-dependent tumours without developing resistance. Through a systematic drug screening approach, we hope to identify promising candidates," explains Dr. Mayor-Ruiz. The project involves evaluating drug candidates in new cellular and animal models developed by the group. These new molecules will undergo preclinical testing and could pave the way for future clinical trials in humans.

Focus: Metastasis metabolism

Cancer cells replicate rapidly and use high amounts of sugar for this process. However, metastatic cells, those with the capacity to escape from the primary tumour and colonise other organs in the body, are fuelled by the metabolism of fats, mainly from palmitic acid. The project undertaken by Dr. Salvador Aznar Benitah, head of the Stem Cell and Cancer laboratory at IRB Barcelona, and Drs. Cristina Saura and Isabel Pimentel, at VHIO, addresses a new way to combat metastatic tumours, namely by directly blocking their energy source.

One of the most urgent metastatic diseases to address is metastatic triple-negative breast cancer, which often does not respond to treatment and has a very poor prognosis. A significant problem is that the disease has different biological bases that vary between patients, thus complicating the search for suitable treatments," explains Dr. Aznar Benitah. The research team will study the relationship between metastatic tumour cells and Schwann cells, which corrupt tissue metabolism around the tumour for its benefit. The overall goal of the project is to identify, at the time of diagnosis, those patients with triple-negative breast cancer who could benefit from a new immunotherapy based on immune metabolic reprogramming instead of (or in addition to) conventional inhibitors.