The TITAN project is among the winners of the European TRANSCAN Joint Transnational Call 2024, launched within the framework of the TRANSCAN-3 partnership, recently established at the European level to strengthen translational cancer research and foster the development of innovative therapeutic strategies. Included in the call dedicated to combination therapies in oncology, the project aims to accelerate the transfer of scientific discoveries from the laboratory to clinical practice, thereby contributing to improved therapeutic options for the most complex and difficult-to-treat cancers.

An international consortium for new therapeutic strategies

TITAN seeks to accelerate the preclinical and translational development of Aurkines – a novel family of chemotherapeutic compounds with significant potential against hard-to-treat solid tumours, with a particular focus on liver cancers.

TITAN, coordinated by Prof. Jesús Bañales and Dr. Pedro Rodrigues, liver cancer biology experts at the Biogipuzkoa Health Research Institute (Donostia/San Sebastian, Spain), brings together an international consortium involving partners from Italy, Spain, France, and the United Kingdom, with expertise ranging from medicinal chemistry and genomics to the development of advanced models for personalized medicine.

The Italian participation is led by Dr. Michela Anna Polidoro, a young researcher at Humanitas Research Hospital and RTD-A at Humanitas University, with the support of the Fondazione Regionale per la Ricerca Biomedica (FRRB). Project activities will be carried out within the Laboratory of Hepatobiliary Immunopathology, directed by Prof. Ana Lleo, Full Professor of Internal Medicine at Humanitas University. The laboratory plays a central role within the consortium thanks to the development of innovative tumor-on-chip models, essential tools for understanding therapeutic response mechanisms and promoting increasingly personalised approaches.

 Humanitas Research Hospital also hosted the project’s kick-off meeting, marking the official launch of the international consortium’s activities within the TRANSCAN-3 program.

A promising therapeutic candidate: the new “Aurkines”

Designed, synthesised, and patented by researchers at Biogipuzkoa Health Research Institute, the University of the Basque Country and the Donostia International Physics Center, Aurkines have already demonstrated validated efficacy across multiple preclinical cancer models, including tumours that had developed resistance following previous cycles of chemotherapy.

Building on this evidence, TITAN aims to assess the antitumour activity of Aurkines both as a monotherapy and in combination with immunotherapy across multiple tumour types, with the aim of broadening their therapeutic reach. To achieve this, the project will employ advanced personalised human models – including cancer-on-chip systems, organoids, and precision-cut tumour slices – that more faithfully reflect the biology of real patient tumours and enable a more rigorous, clinically relevant evaluation of treatment response.

The cholangiocarcinoma-on-chip platform

Within this context, the CCA-on-chip (Cholangiocarcinoma-on-chip) platform plays a key role. This next-generation microfluidic system can reproduce the tumor microenvironment in vitro with remarkable accuracy. The technology enables the study of the biological characteristics of cholangiocarcinoma, its mechanisms of resistance to therapies, and the efficacy of new compounds under conditions that closely mimic human physiology, thereby supporting the development of increasingly targeted and personalized therapeutic strategies.

Translational and international research toward increasingly personalised therapies

Overall, the TITAN project seeks to contribute to the development of new therapeutic strategies for complex cancers, with a particular focus on liver malignancies. As highlighted by Michela Polidoro, “the goal is to generate solid evidence supporting the use of molecules belonging to the Aurkines family both as monotherapy and in combination with other treatments, within the framework of increasingly personalized medicine.”

The project’s approach fully reflects the spirit of the TRANSCAN-3 program, which promotes highly translational and collaborative research capable of integrating clinical and preclinical expertise while facilitating the rapid transfer of scientific results into clinical practice. In this context, the consortium’s international dimension represents a key element for accelerating innovation, harmonizing methodologies, and strengthening the impact of European oncology research.