Dr. Direna Alonso-Curbelo receives an ERC Consolidator Grant to study how inflammation fuels tumor initiation and evolution

The mechanisms underlying the earliest phases of tumor initiation remain enigmatic. While genetic mutations play a critical role, non-genetic factors such as inflammation and epigenetic mechanisms also significantly influence its development. Understanding how these factors interact is essential for advancing the prevention and treatment of this disease.

The European Research Council (ERC) has awarded an ERC Consolidator Grant to Dr. Direna Alonso-Curbelo, head of the Inflammation, Tissue Plasticity & Cancer lab at IRB Barcelona. Backed by funding amounting to €2 M over the next five years, her Project, IGNITE (Unmasking Non-Genetic Determinants Instructing Tumor Initiation), will explore the fundamental mechanisms by which different inflammatory processes drive (or inhibit) the initiation and progression of cancer, taking inflammation-driven pancreatic cancer as a paradigm.

“We want to understand how individual cells perceive and respond to changes in their inflammatory environment,” explains Dr. Alonso-Curbelo. “We hypothesise that different types of inflammation affect cells in distinct ways and that epigenetics plays a key role in shaping the diversity and evolution of these responses.”

Three objectives to unravel non-genetic determinants of  inflammation-driven carcinogenesis

The IGNITE Project revolves around three main goals:

1. Defining how the epigenetic state of pre-cancerous and cancerous cells determines their evolution in response to inflammatory cues.
2. Identifying tissue-level features that differentiate the inflammatory responses that promote cancer from physiological ones that are protective. In addition, new tools will be developed to modulate the states of immune cells associated with each type of inflammation.

 Studying the links between pancreatic cancer risk and systemic inflammatory disorders, aiming to identify pro-tumour mechanisms operating at an organismal level.

The IGNITE project proposes a multidimensional approach spanning cellular, tissue, and organismal levels to explain what drives cancer initiation beyond genetics. This strategy will enable an understanding of how individual cells with distinct epigenetic states sense and respond to inflammatory signals, how these responses impact tissue behaviour, and how tumor-driving cell-environment interactions are impacted by distal inflammatory disorders. By integrating these three levels of analysis, the project aims to unravel the complex interplay between genetic and non-genetic factors that ignite tumor development and progression.

Maximizing the potential of the research

The project requires a multidisciplinary team that will combine experimental models and human sample analysis, applying advanced techniques such as single-cell analysis, cell lineage tracing, and in vivo models.

“The ERC Consolidator Grant allows us to tackle ambitious scientific questions through innovative technologies that would be difficult to implement without this support,” says. Dr. Alonso-Curbelo. “Our team is ready to carry out this project, and we hope our findings will have a significant impact on the field of cancer biology, linking tumor cell plasticity with tissue and organismal physiology.”

Implications for cancer diagnosis and treatment

The results from IGNITE could serve as a starting point for new concepts for the early diagnosis and treatment of pancreatic cancer and, potentially, other inflammation-driven malignancies. By understanding how inflammation and epigenetics interact at different biological levels to influence cancer susceptibility and evolution, it will be possible to develop more specific detection and interception strategies. "We hope our work will contribute to intercepting cancer at earlier stages and harnessing inflammatory signals to steer its progression into clinically more manageable states," concludes the researcher.

About Dr. Direna Alonso-Curbelo

Dr. Direna Alonso-Curbelo studied Pharmacy at the Complutense University of Madrid and completed her PhD at the Spanish National Cancer Research Centre (CNIO) under the supervision of Dr. Marisol Soengas, with short research stays at the Netherlands Cancer Institute (NKI) and Memorial Sloan Kettering Cancer Center (MSKCC). After her PhD, she worked as a postdoctoral researcher in Dr. Scott W. Lowe's laboratory at MSKCC, where she developed innovative experimental models to study tumour-microenvironment interactions. Since 2021, she has led her own research group at IRB Barcelona, focusing on understanding non-genetic mechanisms driving tumour development and progression. In 2024, she was awarded the prestigious "Cancer Discovery Early Career Award" from the American Association for Cancer Research (AACR).
 

More information on the ERC Consolidator Grants: https://erc.europa.eu/news-events/news/erc-2024-consolidator-grants-results