From the creation of the European research area in 2000 to a Mission on cancer in Europe in 2021-lessons learned and implications.

In the year 2000, cancer research in Europe had the potential to make a difference as it had several unique strengths, such as a strong foundation in biomedical science, good patient registries, infrastructures that spanned from biological repositories to bioinformatic hubs as well as thriving Comprehensive Cancer Centers (CCCs) and basic/preclinical cancer research institutions of high international standing. Research, however, was fragmented and lacked coordination. As a result, Europe could not harness its potential for translating basic research discoveries into a clinical setting for the patients' benefit. What was needed was a paradigm shift in cancer research that addressed the translational research continuum. Along these lines, in 2000, European Union (EU) Commissioner Philippe Busquin established the European Research Area (ERA) and in 2002 the European Cancer Research Area (ECRA), and their political approval was a powerful catalyst for the increased involvement of scientists in science policy in the EU. In this report, we briefly describe the actions embraced by the cancer community and cancer organizations in response to Busquin's proposals that led to the creation of the EU Mission on Cancer (MoC) in Horizon 2020 in 2021.

Strategies to decrease inequalities in cancer therapeutics, care and prevention: Proceedings on a conference organized by the Pontifical Academy of Sciences and the European Academy of Cancer Sciences, Vatican City, February 23-24, 2023.

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA-Cancer Moonshot and the EU-Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state-of-the-art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost-effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost-effective healthcare.

The Porto European Cancer Research Summit 2021.

Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high-quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures - namely translational research, clinical/prevention trials and outcomes research - were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next-generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health-related quality-of-life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU-wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost.

Towards a cancer mission in Horizon Europe: recommendations.

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice.

Cancer Core Europe: A translational research infrastructure for a European mission on cancer.

Cancer Core Europe is a European legal alliance consisting of seven leading cancer centres - most of them Comprehensive Cancer Centres (CCCs) - with a single portal system to engage in various research projects with partners. Cancer Core Europe was established to create a sustainable, high-level, shared research infrastructure platform hosting research collaborations and task forces (data sharing, clinical trials, genomics, immunotherapy, imaging, education and training, and legal and ethical issues), with a controlled expansion agenda. Translational cancer research covers the cancer research continuum from basic to preclinical to early clinical, late clinical, and outcomes research. Basic-preclinical research serves as the 'engine' for early clinical research by bridging the early translational research gap and is the primary and current focus of the consortium as exemplified by the launching of the Basket of Baskets trial, Europe's largest precision cancer medicine trial. Inspired by the creation of Cancer Core Europe, the prevention community established Cancer Prevention Europe, a consortium of ten cancer prevention centres aimed at supporting the complete prevention research continuum. Presently, Cancer Core Europe and Cancer Prevention Europe are integrating therapeutics and prevention strategies to address in partnership the widening cancer problem. By providing innovative approaches for cancer research, links to healthcare systems, development of quality-assured multidisciplinary cancer care, and assessment of long-term outcomes, the virtual infrastructure will serve as a hub to connect and interact with other centres across Europe and beyond. Together, Cancer Core Europe and Cancer Prevention Europe are prepared to function as a central engine to tackle, in collaboration with various partners, a potential 'mission on cancer' addressing the cancer burden.

Towards a mission-oriented approach to cancer in Europe: an unmet need in cancer research policy.

Today, cancer is a significant challenge for society, healthcare systems and the growing number of affected patients and their families. This article argues that new paradigms and conditions for responsible science and innovation policy across the European Union (EU) require (i) the collective action of Research & Development institutions, (ii) a system approach to health systems, higher education and patient organizations, and (iii) new initiatives to encourage international cooperation across an enlarged Europe; no single country can successfully fight the disease(s) on its own. Recently, a cancer mission was proposed (Celis and Pavalski, ), the origins of which are rooted in the continuous efforts of the research community, cancer patient organizations, member states and the European Commission during nearly two decades to address the fragmentation and lack of coordination of European cancer research; these efforts led to the creation of Cancer Core Europe and Cancer Prevention Europe, consortia aimed at linking therapeutic and prevention geometries. Ultimately, the platform/infrastructure will be composed of networks of Comprehensive Cancer Centres and cancer research centres across Europe to reach the critical mass of expertise, patients and collaborative portfolio of projects that are necessary to promote science-driven and social innovations in the era of personalized (precision) cancer medicine. Employing a mission-oriented approach to achieve the goal of ensuring a long life expectancy for three out of four cancer patients by 2030 is likely to have a particularly positive impact on the way European citizens' value science and knowledge. It will change the lives of many families across Europe and beyond and should be oriented to ensure that Europe is at the forefront when it comes to quality of life. It is our collective responsibility to ensure that not a single person or region in Europe is left behind.

European Academy of Cancer Sciences - position paper.

The European Academy of Cancer Sciences (EACS) is an independent advisory body of well-recognised medical specialists and researchers striving to create a compelling interactive continuum of cancer research, from innovative basic research to implementation of state-of-the-art evidence-based cancer care and prevention. Achieving the above will entail bridging high-quality basic and preclinical cancer research to research on prevention, early detection and therapeutics as well as improving coordination of translational research efforts across Europe. The latter is expected to be expedited through quality assuring translational cancer research in Comprehensive Cancer Centres - entities that link research with the healthcare system - and networks of cancer research centres. Achieving a critical mass of expertise, resources and patients is crucial. Improving late translational research, which involves clinical studies to assess effectiveness, and added value for the health care is also a high priority. Both high-quality Big Data collections and the intelligent use of these data will promote innovation in cancer research and support outcomes research to assess clinical utility, quality of cancer care and long-term follow-up of treated patients. The EACS supports the mission-oriented approach recently proposed by the European Commission in Horizon Europe to deal with major challenges and would like to persuade the EU and its member states to formally launch a mission in cancer to boost and streamline the cancer research continuum in Europe. Building a coherent translational cancer research continuum with a focus on patients and individuals at risk will require, however, foresight as well as the extensive and continuous provision of evidence-based advice to inform policy.

Up-regulated proteins in the fluid bathing the tumour cell microenvironment as potential serological markers for early detection of cancer of the breast.

Breast cancer is by far the most common diagnosed form of cancer and the leading cause of cancer death in women today. Clinically useful biomarkers for early detection of breast cancer could lead to a significant reduction in mortality. Here we describe a detailed analysis using gel-based proteomics in combination with mass spectrometry and immunohistochemistry (IHC) of the tumour interstitial fluids (TIF) and normal interstitial fluids (NIF) collected from 69 prospective breast cancer patients. The goal of this study was to identify abundant cancer up-regulated proteins that are externalised by cells in the tumour microenvironment of most if not all these lesions. To this end, we applied a phased biomarker discovery research strategy to the analysis of these samples rather than comparing all samples among each other, with inherent inter and intra-sample variability problems. To this end, we chose to use samples derived from a single tumour/benign tissue pair (patient 46, triple negative tumour), for which we had well-matched samples in terms of epithelial cell numbers, to generate the initial dataset. In this first phase we found 110 proteins that were up-regulated by a factor of 2 or more in the TIF, some of which were confirmed by IHC. In the second phase, we carried out a systematic computer assisted analysis of the 2D gels of the remaining 68 TIF samples in order to identify TIF 46 up-regulated proteins that were deregulated in 90% or more of all the available TIFs, thus representing common breast cancer markers. This second phase singled out a set of 26 breast cancer markers, most of which were also identified by a complementary analysis using LC-MS/MS. The expression of calreticulin, cellular retinoic acid-binding protein II, chloride intracellular channel protein 1, EF-1-beta, galectin 1, peroxiredoxin-2, platelet-derived endothelial cell growth factor, protein disulfide isomerase and ubiquitin carboxyl-terminal hydrolase 5 were further validated using a tissue microarray containing 70 malignant breast carcinomas of various grades of atypia. A significant number of these proteins have already been detected in the blood/plasma/secretome by others. The next steps, which include biomarker prioritization based on the hierarchal evaluation of these markers, antibody and antigen development, assay development, analytical validation, and preliminary testing in the blood of healthy and breast cancer patients, are discussed.