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.

Editorial.

May 2020 be a rewarding year of change. The recent commitment of the European Commission and policymakers to fight cancer in partnership is expected to bring forward the changes long required in the field. Molecular Oncology will stay at the forefront of all developments in the area of oncology by providing a flexible platform for European and International cancer research.

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.

Cancer Core Europe: A European cancer research alliance realizing a research infrastructure with critical mass and programmatic approach to cure cancer in the 21st century.

Translational cancer research covers the whole cancer research continuum from basic to preclinical to early clinical, late clinical and outcomes research. Basic-preclinical research is the "engine" for early clinical research bridging the early translational research gap. Cancer Core Europe has been created to construct a sustainable, high level, shared research infrastructure platform with research collaborations and taskforces (data sharing, clinical trials, genomics, immunotherapy, imaging, legal & ethical problems, and education & training) having representatives from all seven member centres, in a controlled expansion model. In parallel, a consortium of ten cancer prevention centres was established, Cancer Prevention Europe, to support the complete cancer prevention research continuum. Cancer Core Europe is launching at present the Basket of Baskets trial, which is the largest personalized cancer medicine trial effort in Europe. At present, Cancer Core Europe and Cancer Prevention Europe are in the process of integrating therapeutics and prevention strategies to address in partnership the increasing cancer problem. By offering innovative approaches for cancer research, links to the healthcare systems, development of quality-assured multidisciplinary cancer care, as well as the assessment of long-term outcomes, the infrastructure is expected to serve as a hub to connect with other centres in Europe as well as on other continents. In this manner Cancer Core Europe and Cancer Prevention Europe prepare to tackle the "Mission on Cancer", with infrastructure and proofs of concept for therapeutics and prevention, research for assessment of effectiveness, health economics and added value for patients and the healthcare systems.

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.

A mission-oriented approach to cancer in Europe: a joint mission/vision 2030.

By combining innovative prevention and treatment strategies in a sustainable state-of-the-art virtual European cancer centre/infrastructure, it will be possible by 2030 to achieve a long-term survival of 3 out of 4 cancer patients in countries with well-developed healthcare systems. Furthermore, the proposed concerted actions will pave the way to handling the economic and social inequalities in countries with less developed systems. These efforts will also ensure that in the long-run, science-driven and social innovations reach patients across the healthcare systems in Europe.

Shaping science policy in Europe.

The Lisbon Strategy was adopted by the Heads of State and Government of the European Union (EU) in 2000. By moving science into a central position for the development of a European knowledge-based economy and society, its adoption at political level seems to have been a powerful catalyst for the increased involvement of scientists in science policy in the EU. Recognising the need for scientists to act collectively in order to contribute to shape the future of science policy in Europe, a pioneering group of European science organisations leaders and representatives, as well as other scientists, initiated a European, interdisciplinary, inclusive movement leading to the creation of the European Research Council (ERC) to support basic research of the highest quality. Having scientists' campaign for the funding of bottom-up research by the EU Framework Programmes exclusively on scientific grounds, and for an ERC, was a unique event in the recent history of European science policy. For the first time, the scientific community acted collectively and across disciplinary or national boundaries as a political actor for the sake of a better science policy for Europe. As is often the case when first-hand experience is gained through the creation of a new organization, novel forms of collaboration arise. The European biomedical community has recently proposed the creation of a strategic action plan for health research (the European Council of Health Research; EuCHR), provisionally translated at present into a Scientific Panel for Health (SPH) research in Horizon 2020, the EU's research-funding programme for the period 2014-2020. The creation of such Scientific Panel should be viewed as an important contribution by the biomedical community as a major political agreement has been reached on the need for a comprehensive and long-term scientific strategy to accelerate research and facilitate innovation at EU level. It is our belief that describing and analyzing the process leading to the creation of the ERC and SPH (2002-2014) should be widely shared with the research community in general, as this may contribute to the understanding of the evolving relations between scientists and science-policy making.

A personal account of the early stages of proteomics at Aarhus University.

This article is part of a Special Issue entitled: 20 years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.

Proteomic profiling of triple-negative breast carcinomas in combination with a three-tier orthogonal technology approach identifies Mage-A4 as potential therapeutic target in estrogen receptor negative breast cancer.

Breast cancer is a very heterogeneous disease, encompassing several intrinsic subtypes with various morphological and molecular features, natural history and response to therapy. Currently, molecular targeted therapies are available for estrogen receptor (ER)(-) and human epidermal growth factor receptor 2 (Her2)-positive breast tumors. However, a significant proportion of primary breast cancers are negative for ER, progesterone receptor (PgR), and Her2, comprising the triple negative breast cancer (TNBC) group. Women with TNBC have a poor prognosis because of the aggressive nature of these tumors and current lack of suitable targeted therapies. As a consequence, the identification of novel relevant protein targets for this group of patients is of great importance. Using a systematic two dimensional (2D) gel-based proteomic profiling strategy, applied to the analysis of fresh TNBC tissue biopsies, in combination with a three-tier orthogonal technology (two dimensional PAGE/silver staining coupled with MS, two dimensional Western blotting, and immunohistochemistry) approach, we aimed to identify targetable protein markers that were present in a significant fraction of samples and that could define therapy-amenable sub-groups of TNBCs. We present here our results, including a large cumulative database of proteins based on the analysis of 78 TNBCs, and the identification and validation of one specific protein, Mage-A4, which was expressed in a significant fraction of TNBC and Her2-positive/ER negative lesions. The high level expression of Mage-A4 in the tumors studied allowed the detection of the protein in the tumor interstitial fluids as well as in sera. The existence of immunotherapeutics approaches specifically targeting this protein, or Mage-A protein family members, and the fact that we were able to detect its presence in serum suggest novel management options for TNBC and human epidermal growth factor receptor 2 positive/estrogen receptor negative patients bearing Mage-A4 positive tumors.

Tissue proteomics of the human mammary gland: towards an abridged definition of the molecular phenotypes underlying epithelial normalcy.

Our limited understanding of the biological impact of the whole spectrum of early breast lesions together with a lack of accurate molecular-based risk criteria for the diagnosis and assignment of prognostic significance to biopsy findings presents an important problem in the clinical management of patients harboring precancerous breast lesions. As a result, there is a need to identify biomarkers that can better determine the outcome of early breast lesions by identifying subpopulations of cells in breast premalignant disease that are at high-risk of progression to invasive disease. A first step towards achieving this goal will be to define the molecular phenotypes of the various cell types and precursors - generated by the stem cell hierarchy - that are present in normal and benign conditions of the breast. To date there have been very few systematic proteomic studies aimed at characterizing the phenotypes of the different cell subpopulations present in normal human mammary tissue, partly due to the formidable heterogeneity of mammary tissue, but also due to limitations of the current proteomic technologies. Work in our laboratories has attempted to address in a systematic fashion some of these limitations and here we present our efforts to search for biomarkers using normal fresh tissue from non-neoplastic breast samples. From the data generated by the 2D gel-based proteomic profiling we were able to compile a protein database of normal human breast epithelial tissue that was used to support the biomarker discovery program. We review and present new data on the putative cell-progenitor marker cytokeratin 15 (CK15), and describe a novel marker, dihydropyriminidase-related protein 3 (DRP3) that in combination with CK15 and other well known proteins were used to define molecular phenotypes of normal human breast epithelial cells and their progenitors in resting acini, lactating alveoli, and large collecting ducts of the nipple. Preliminary results are also presented concerning DRP3 positive usual ductal hyperplasias (UDHs) and on single cell layer columnar cells (CCCs). At least two bona fide biomarkers of undifferentiated ERα/PgR negative luminal cells emerged from these studies, CK15 and c-KIT, which in combination with transformation markers may lead to the establishment of a protein signature able to identify breast precancerous at risk of progressing to invasive disease.