The 7 IRB Barcelona projects that have been awarded funding seek to advance research into cancer, with a focus on the cancer patient and increasing survival rates.
To this end, the grants support talented researchers, thus ensuring employment stability; drive clinical research to involve medical professionals in research, and thus bring results closer to patients; and back innovation through specific support.
The Spanish Association Against Cancer (Spanish acronym AECC) has presented its 2021 Research Grants in an event held at the organisation’s headquarters in Barcelona. Five laboratories at IRB Barcelona have received 1 or 2 grants in the following categories: Seed Ideas; Coordinated Projects; AECC Lab: and AECC Researcher.
This year, to contribute to the advancement of cancer research focused on the patient and increasing survival rates, the AECC has provided 186 projects with around €20M.
Mechanism of resistance to chemotherapy in triple-negative breast cancer – AECC Coordinated Project, Dr. Ángel R. Nebreda (€1.2M)
Regarding deaths caused by cancer, breast cancer is ranked in second place in women, and around 30,000 cases are diagnosed in Spain each year. The most aggressive type of breast cancer is known as triple-negative, and it does not have any specific weak spot and is therefore treated with standard chemotherapy, usually taxanes and anthracyclines. However, some patients do not respond to these treatments and end up developing resistance and metastasis, which is the main cause of death.
The AECC Coordinated Project led by Dr. Ángel Nebreda, head of the Signalling and Cell Cycle laboratory at IRB Barcelona, will target the mechanisms underlying resistance to chemotherapy. It seeks to determine characteristics that can predict patient response, as well as identify potential targets to strengthen the effect of existing drugs, and define new therapeutic strategies.
Lasting 5 years, the project will be developed in collaboration with Dr. Juan Miguel Cejalvo (Instituto de Investigación Sanitaria (INCLIVA) in Valencia), Dr. Ignacio Varela (University of Cantabria), and Dr. Fernando Calvo (Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC-CSIC).
Tumour senescence as a therapeutic target – AECC Coordinated Project, Dr. Manuel Serrano (€1.2M)
Senescence is a cell state related to ageing, in which—through cell damage or stress—cells stop dividing but do not die, thus remaining in the body. Current cancer treatments cause a large number of senescent cells inside tumours. These cells are known to support the survival and growth of treatment-resistance cancer cells. Laboratory experiments have already shown that the removal of senescent cells from the tumour considerably boosts the effectiveness of cancer treatments.
The AECC Coordinated Project led by Dr. Manuel Serrano, head of the Cellular Plasticity and Disease laboratory at IRB Barcelona, will address the development of non-invasive techniques to detect senescence in patients’ tumours and find new drugs or combinations that neutralise senescent cells, thereby improving the efficacy of current treatments.
Spanning 5 years, this project will be developed in a consortium involving Dr. María Abad, Dr. Raquel Pérez-López and Dr. Joaquín Mateo, all three from the Vall d'Hebron Institute of Oncology (VHIO).
Exploiting cellular mechanisms to innovate in the discovery of drugs and cancer treatments – AECC Lab, Dr. Cristina Mayor-Ruiz (€300,000)
A human cell contains thousands of different proteins that have key functions as accelerators of chemical reactions or the determinants of the shape and structure of our cells. The cell regulates its protein levels by marking those that are unwanted with a label, which consists of the binding of another small protein called “ubiquitin”. Labelled proteins are then rapidly degraded in cell crushers known as "proteasomes”.
The AECC Lab project headed by Dr. Cristina Mayor-Ruiz at IRB Barcelona will explore how to block this protein degradation pathway to attack cancer cells and thus increase the survival of cancer patients. Specifically, in collaboration with Dr. César Serrano at the Vall d'Hebron Institute of Oncology (VHIO), new therapeutic strategies for acute myeloid leukaemia (AML) and gastrointestinal stromal tumour (GIST) will be probed.
Eliminating chemotherapy-induced senescent cells – AECC Researcher, Dr. José Alberto López (€100,000)
Chemotherapy causes the appearance of senescent cells in the tumour and also in healthy tissues. These cells survive for long periods and contribute to cancer relapse after treatment.
The AECC Researcher project, which will be developed by Dr. José Alberto López over 2 years in IRB Barcelona’s Cellular plasticity and Disease laboratory, headed by Dr. Manuel Serrano, aims to facilitate the removal of these senescent cells by the immune system. It will also explore ways to detect senescent cells in patients.
The male hormone receptor and its involvement in castration-resistant prostate cancer – AECC Postdoctoral Grant, Dr. Borja Mateos (€85,000)
The recurrence of prostate cancer after hormone treatment is fairly common. Most of these treatments target the androgen (male hormones) receptor and cancer cells. However , through the accumulation of mutations, cancer cells modify the structure of the receptor and prevent the binding of inhibitor drugs, thus bringing about resistance to treatment.
Supported by the AECC Postdoctoral Grant, Dr. Borja Mateos, a member of IRB Barcelona’s Molecular Biophysics laboratory, headed by Dr. Xavier Salvatella, will focus on producing new molecules that block the androgen receptor by binding to a flexible region in this protein to which current drugs are unable to bind.
Mutagenic tRNA molecules for the treatment of pancreatic cancer – AECC Seed Idea, Dr. Lluís Ribas (€20,000)
Pancreatic cancer is one of the most aggressive types of cancer, and most patients who suffer from this disease die from it because tumours are diagnosed too late when they can no longer be removed.
Through this AECC Seed Idea project, Dr. Lluís Ribas’ laboratory at IRB Barcelona will explore the use of viral therapy against these tumours, using modified viruses to infect and eliminate cancer cells. To this end, they will use tRNA molecules that cause mutations in specific regions of the cancer cells. Lasting two years, this project will be developed in the framework of a wider collaboration effort with the Hospital Clínic (IDIBAPS) and the Vall d'Hebrón Hospital (VHIO) in Barcelona.
Overcoming resistance to targeted protein degradation in cancer treatments – AECC Seed Idea, Dr. Cristina Mayor-Ruiz (€20,000)
Despite tremendous progress in drug discovery, more than 80% of the proteins in our bodies are inaccessible to traditional drugs because they do not have cavities to which they can bind. PROTACs provide a novel pharmacological approach since they use the cell’s own protein destruction machinery to trigger the degradation of proteins that are relevant for cancer treatment. PROTAC technology has experienced marked progress in recent years; however, because this technology is in its infancy, some aspects are not yet known in depth.
The AECC Seed Idea project headed by Dr. Cristina Mayor-Ruiz will study the mechanisms underlying resistance to treatment with PROTACs (which have already been observed in the laboratory). The project aims to anticipate problems that may arise now that these drugs are starting to be administered to patients.