Cancer as the second leading cause of death in Europe poses an escalating challenge that needs urgent action. Translational cancer research should be the primary focus for addressing the increasing cancer burden in Europe and counteracting the present main strategy to convert cancer to a chronic disease. From a policy perspective, the translational cancer research continuum should be strengthened. The EU Mission on Cancer (MoC), alongside Europe's Beating Cancer Plan (EBCP), should be revisited to prioritize prevention, early detection, and improved treatment with a focus on increasing cure rates and enhancing patients' quality of life, especially for those with incurable disease. The MoC should be strengthened through long‐term, sustainable funding of competitively selected Comprehensive Cancer Centers (CCCs) integrating cancer care, health care dependent prevention, research, and education across Europe to ensure stewardship by problem owners. This is critical to avoid the traditional, fragmented “short‐term, project‐based funding” structure of the European Commission's collaborative research, which relies on many small projects dispersed across varied institutional contexts. Articulation with frontier research in Europe, supported by the European Research Council (ERC), and with critical innovations, including those sponsored by the European Innovation Council (EIC), becomes paramount. The current goal to establish around 100 CCCs is highly commendable, with each CCC and related networks targeting between 3.5 and 4 million people, following adequate accreditation procedures. In addition, the political ownership of the MoC should ensure adequate coordination/integration with the EBCP, together with appropriate engagement and responsibility on the part of national and European authorities to address policy and implementation actions. In summary, our policy analysis recommends establishing a coherent cancer research continuum to drive therapeutic innovation and strengthen prevention.

The cancer problem is expanding, particularly in low‐ and middle‐income countries (LMICs). Preventive measures can reduce the incidence by 40–50%, and cure rates have increased during the past decades in a number of cancers. However, optimizing prevention programmes and increasing cure rates of cancer remain significant research challenges. The main focus of the conference was on P4 Cancer Medicine (Predictive, Preventive, Personalized and Participatory), a comprehensive strategy encompassing Health‐Related Quality of Life (HRQoL) research, aiming to enhance the well‐being of patients and individuals at risk. Addressing the cancer problem requires two key elements: translational cancer research and the development of relevant infrastructures. A Comprehensive Cancer Centre (CCC) acts as an innovation hub by integrating high‐quality, multidisciplinary therapy and care, with healthcare‐dependent prevention, research, and education. The United States has been at the forefront, providing quality‐assured CCCs and the Cancer Moonshot for strategic cancer research. The EU has followed with the European Research Council for basic research, the European Innovation Council to boost disruptive innovation, and two EU initiatives on cancer, Europe's Beating Cancer Plan (EBCP) and the Mission on Cancer. The increasing complexity of cancer biology and technologies presents both a research challenge and a healthcare demand. For most patients, a CCC is not available. A critical discussion focused on quality assurance of healthcare outside the catchment area of a CCC and involving patients in clinical research. The strategic deployment of resources to support collective healthcare efforts and research aimed at reducing the cancer problem was discussed with representatives from the United States, EU, Africa, China, India and Taiwan. Analyses of translational cancer research have revealed important gaps in implementing innovations, assessment of clinical effectiveness, HRQoL, outcome and health economics research. The increased release of new anticancer agents over the last 25 years, accompanied by insufficient information on clinical benefits, presents both an economic and ethical problem. Direct healthcare costs have increased due to expenses for anticancer agents for the treatment of patients with incurable diseases. Evidence‐based treatment based on HRQoL research is an unmet need. Basic/preclinical research aimed at increasing the cure rate should identify new, broader targets for therapy and develop extended diagnostic technologies for stratifying patients, to inform innovative clinical trials. Present research strategies convert cancer to a chronic disease, a growing burden for the healthcare systems. The increasing complexity of cancer biology and technology, the growing need for translational cancer research, and the demand for supporting infrastructures underscore the importance of international collaborations between CCCs. However, funding for cancer research is not currently aligned to reduce the cancer problem. While public funding for cancer research doubled between 2005 and 2024, the pharmaceutical industry's spending on cancer research increased tenfold. Increasing funding by public and non‐profit funding organizations is mandatory. Education is another significant need, but it is currently fragmented and underfunded. The last session of the conference summarized the strategies in a Statement with a strong emphasis on global collaboration addressing the growing cancer burden and pronounced inequalities. Expanding partnerships and fostering innovative, multidisciplinary approaches to cancer prevention, therapeutics/care, as well as research, are not just urgent but essential steps towards reducing incidence, increasing cure rates and enhancing the well‐being of cancer patients. Data‐driven cancer medicine is currently under development, and modern communication technologies for diagnostics may facilitate interactions across geographical distances. A global cancer research agenda can become a model of solidarity, sustainability, and ethical responsibility.

The development of new anticancer treatments, their clinical evaluation and introduction into the healthcare system need improvement. New drugs and cell therapies often come with significant costs for society while only marginally improving patients' survival and health-related quality-of-life. Therefore, bold, innovative clinical trials with critical assessment of the efficacy and cost-effectiveness of new preventive measures and medical treatments are needed to ensure that patients and society benefit. Drug development programmes controlled by pharma should be complemented with initiatives such as stop studies, dose reduction, combination and repurposing trials. These should be validated in academia-initiated trials supported by societal funds. Special attention should be devoted to paediatric and rare adult cancers. Comprehensive Cancer Centres (CCCs) covering the entire cancer research continuum, present throughout the EU, are critical for this. More of such centres must be established concomitantly with a robust accreditation methodology to ensure that they meet appropriate quality standards. It is crucial that funding for these initiatives, now temporarily and partially provided by the EU Cancer Mission and Europe's Beating Cancer Plan, is secured for a much longer period.

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.

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.

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.

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation.

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.

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.

1 The Netherlands Cancer Institute, Amsterdam, The Netherlands 2 European Academy of Cancer Sciences 3 Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden 4 Gustave Roussy Cancer Campus Grand Paris, Villejuif, France 5 German Cancer Research Center (DKFZ), Heidelberg, Germany 6 German Cancer Consortium (DKTK), Heidelberg, Germany 7 Charite-Universitatsmedizin, Berlin, Germany 8 International Agency for Research on Cancer (IARC/WHO), Lyon, France 9 Swiss Institute for Experimental Cancer Research (ISREC), Federal Institute of Technology in Lausanne (EPFL), and Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland 10 EORTC Headquarters, Brussels, Belgium 11 European Cancer Patient Coalition, Brussels, Belgium 12 Cancer Research UK Cambridge Centre, UK 13 Organisation of European Cancer Institutes (OECI) 14 Institut Curie, Paris, France 15 Medical Oncology Department, Vall d’Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Spain 16 Danish Cancer Society Research Centre, Copenhagen, Denmark

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.

The main components of the cancer research continuum are basic/preclinical research, early and late clinical research and, after the adoption of an innovation by the healthcare or health organisations, outcomes research. Translational cancer research, defined as a coherent cancer research continuum, is mandatory to address the increasing burden of cancer effectively. The growing cancer problem can only be significantly modified by concerted action involving prevention to decrease incidence, early detection and treatment to increase the cure rate, and personalised/precision cancer medicine to adapt early detection and treatment to the biology of a tumour with the aim of increasing the cure rate, prolonging survival and improving health-related quality of life. By definition, translational cancer research for therapeutics has a focus on patients' needs and for prevention for individuals at-risk. Consequently, to increase the effectiveness of translational research, the different components of the cancer research continuum need to be better connected to the fundamental aim of a mission-oriented approach to cancer (Celis and Pavalkis, ).

The expansion of knowledge in the area of cancer biology which has taken place over the last 40 years has profoundly influenced clinical cancer research and made high-quality multidisciplinary cancer care imperative. In the United States, Comprehensive Cancer Centres (CCCs) have existed for a long time. To enhance their effectiveness and quality, the National Cancer Institute (NCI) has developed an accreditation methodology for CCCs [ [1] https://www.cancer.gov/research/nci-role/cancer-centers. Google Scholar ]. NCI-designated CCCs are characterised by innovative high-quality cancer research covering the complete trajectory—from basic to clinical research, as well as dissemination of acquired knowledge. The designated CCCs are sustained with earmarked financial support from the NCI to accelerate innovation. In some European countries like France, Italy and The Netherlands, cancer research and cancer care have been organised in CCCs. However, there was no existing accreditation methodology built on generally accepted criteria for integrating cancer care and prevention with research and education.

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.

Purpose National Cancer Control Plans (NCCPs) often describe structural requirements for high quality cancer care. During the fourth European Roundtable Meeting (ERTM) participants shared learnings from their own national setting to formulate best practice in optimizing communication strategies between parties involved in clinical cancer registries, cancer centers and guideline groups. Results A decentralized model of data collection close to the patient and caregiver enhances timely completion and the quality of the data captured. Nevertheless, central coordination is necessary to define datasets, indicators, standard settings, education, training and quality control to maintain standards across the network. In particular, interaction of parties in cancer care network has to be established and maintained on a regular basis. Conclusion After establishing the structural requirements of cancer care networks, communication between the different components and parties is required to analyze outcome data, provide regular reporting to all and develop strategies for continuous improvement of quality across the network.

Professor Thomas Tursz, born in Krakow, Poland, in 1946, died on April 27. He was Professor of Oncology at the Faculty of Medicine Paris-Sud since 1986 and General Director of the Institut Gustave Roussy (1994–2010). Thomas was the leader of the French Doctoral School of Oncology which he founded in 1999, and President of the French Federation of Comprehensive Anticancer Centres (FNCLCC) from 2004 to 2010. He was highly involved in the European Organization for the Research and Treatment of Cancer (EORTC) as both Chairman of the Scientific Advisory Committee (2003–2006) and Vice President of the Board (2006–2009). His experience as President of the FNCLCC was crucial for the Organization of European Cancer Institutes (OECI) when he acted as President from 2002 to 2005. Thomas acquired basic experience of tumour biology when he was a postdoc in George Klein0s laboratory at the Karolinska Institutet (KI). He had a particular interest in the biology of virus-induced tumours as well as immunological responses including the role of thioredoxin in lymphocytes infected by Epstein–Barr virus. From 1994 to 1996, he acted as President of the International Association for Research on Epstein–Barr virus and Associated Diseases. In the clinical research area, he conducted a number of important clinical trials in breast cancer, lung cancer and soft-tissue sarcomas. He had a particular interest in cytokines and gene therapy, and his clinical research activities were further disseminated to the European level when he was the Chairman of the Sarcoma Group of the EORTC (1993–1996). Thomas received several prestigious awards such as the Prix de Canc erologie from the French National League Against Cancer (1979), the Bernard-Halpern Immunology Award (1983), the Rosen Oncology Award (1989), the Grand Prix in Oncology from the Academy of Medicine (1992), the Hamilton Fairley Award for clinical research (1998) and the Prix de Rayonnement Franc ais (2001). He was the author of 350 international scientific publications. Thomas was also an esteemed member of the Editorial Board of Molecular Oncology ever since its creation in 2007. As a close friend, Thomas was a fascinating person. He was well educated in humanistic disciplines with a specific interest in art, literature and politics. His marvellous sense of humour together with his vast experience in both basic biology and clinical oncology made him a visionary with a comprehensive vision for the future of patients with cancer and oncology in general. Already 18 years ago, we had discussions about the need for the strategic development of oncology based on modern cancer biology aimed at translational research. It was quite clear for Thomas that the present organizations involved in cancer care and research must be adapted to modern biology by improving the multidisciplinary structure of cancer care and qualityassured translational cancer research environments. On the board of the OECI, his argumentation for creating a European methodology for designation of Comprehensive Cancer Centres (CCCs) was convincing, and as a result, a procedure was put in place in 2007. Thomas was aware of the lack of critical mass in cancer research centres concerning advanced technological resources as well as patients and competencies, and he argued for formal collaborations between

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.

Implementing technical guidelines and standards as well as ways to boost cooperation should facilitate sharing of hospital biobank samples.

The cancer burden is increasing globally due in large part to the ageing of the population. A major challenge for healthcare systems is an increasing population of cancer patients who are not cured but are living longer with their cancer, making cancer into one of the major chronic diseases and one that carry a high economic burden due to the high cost of many cancer therapies. Innovative approaches to cancer prevention will be able to decrease some of these challenges. Developing better treatment strategies for disseminated disease remains one of the main goals to modify the growing patient population with chronic cancer disease. This means that prolonged survival during treatment must be converted to an improved cure rate. The rapid development of knowledge in cancer biology continually changes the challenges for therapeutic research. There is a shift from selection of therapies based on the histologic origins of tumours to alterations of the cancer genome as targets for more specific anticancer drugs, molecularly targeted agents, and immunotherapies. The large number of genetic and epigenetic alterations driving tumour cells creates a number of subsets within each histologic tumour type. This results in a large inter-patient variation, and in the end there may be thousands of tumour types with specific molecular backgrounds requiring unique treatments. Further, genomic instability makes the problem still more complex, producing tumour cell heterogeneity and intra-patient variation. When considering combinations of anticancer treatments for the heterogeneous population of tumours the number of treatment possibilities is enormous, more than existing cancer patients. New strategies for therapeutic research are therefore urgently needed to enable the most efficient process of drug development. Personalized or precision cancer medicine aims at “the right treatment for the right patient at the right time”. This means individualized treatment with the optimal anticancer agent(s) delivered with optimal dose and scheduling. To achieve this, biomarker research is fundamental. We need to know who should be treated (early detection of disease), prognosis, and how to predict likely treatment outcomes in terms of both anti-tumour activity and side-effects. Biomarker translational research involves biomarker discovery and analytical and clinical validation, as well as assessment of clinical utility. Biological cancer research is supporting clinical trials with large numbers of potentially valuable biomarkers. The connection, however, between discovery and clinical validation of biomarkers is still at an early stage. Currently there are few molecular diagnostic tests recommended by major regulatory and advisory bodies. Reliable methods for assessment of biomarkers for clinical use are discussed in this issue of Molecular Oncology. Conceptual developments based on increasing knowledge of cancer biology suggest changes in the methodology for clinical trials. This issue aims at highlighting some of the problems and challenges for clinical trials methodology when moving into personalized cancer medicine. The traditional strategy involving phase I–III trials with determination of efficacy based on the results of large comparative clinical studies is no longer possible in many situations. Traditional trials focus on large patient populations, while identification of many subgroups of cancer patients results in the need for smaller and more focused clinical trials with preselected patients based on the biomarkers in their cancers. Histology-based trials with enrichment for patients with specific molecular alterations represent a step forward. New trial methodologies are being developed such as basket, platform, “N-of-1”, and adaptive trials. More informative ways to describe individual patient tumour responses are under development like waterfall, spider and swim plots. Understanding of mechanisms behind inter- and intra-patient heterogeneity, including inherited and acquired drug resistance, is fundamental for future biological research and the design of a new generation of clinical trials. Drug development needs to be better coordinated with biomarker research. Omics technologies with bioinformatics support must deliver data in real time for treatment. Technologies to stratify tumours and patients must be validated and reporting language must be harmonised, so that data from different centres can be compiled and compared. Biological changes in the tumours during the course of treatment must be followed with repeated biopsies and treatment adapted based on the evolving genomic landscape of the tumour. Technologies for liquid (blood) biopsies will expand. Imaging technologies will increase in importance, not only to describe the extent and heterogeneity of the disease, but also to assess early response after treatment, fluctuations of expression of biomarkers within the tumours, as well as target saturation. Improving dose finding in early phase clinical trials is a specific problem. Molecularly targeted agents and immunotherapies may have toxicities which often are not dose dependent. Pharmacokinetic and pharmacodynamic outcomes together with functional imaging are being explored to obtain the optimal biological dose and schedule of treatment, i.e., continuous or intermittent. Animal models (genetically engineered mouse models and patient derived xenografts) are important sources of biological information when designing early phase clinical trials. Mouse trials performed in parallel with human trials, co-clinical studies, are under development in order to identify the relevant biological information needed for early clinical trials. A separate issue on animal models in cancer research was recently published in this journal (Berns and Barbacid, 2013). Comparative (randomized) clinical trials will be more difficult to conduct and observational (not randomized) studies and adaptive trials will play an increasing role in determining the efficacy of new treatments. Assessments of clinical effectiveness and cost-effectiveness are today unmet needs, and the gap between clinical efficacy, which is the outcome from a clinical trial, and clinical effectiveness, which is the outcome when a total population of patients is treated, must be bridged. Documentation of antitumour response will need fairly small patient groups, while assessment of side-effects will need larger groups of patients, more heterogeneous populations and long-term follow-up. It is important that clinical research and clinical practice become better integrated. The Patient Generated Health Data initiative offers a possibility to collect “big data” for observational studies at the population-level. A new generation clinical trials with companion diagnostics will require addressing and modernizing regulatory policies to keep pace with scientific innovation. The need for agreement between academic centres, the pharmaceutical industry and regulatory authorities regarding evidence and assessment of the balance of benefit-risk must be addressed. For all of these reasons, clinical trials methodology, when moving into personalized cancer medicine, is a complex and expanding area. This issue of Molecular Oncology addresses some of the important areas under development. We have added a chapter on cancer prevention which is developing towards identification of high risk individuals and treatment of stratified high risk groups, based on benefit-risk assessments that can present new challenges. Recently there have been separate articles in this journal about targeted drugs and resistance mechanisms (Groenendijk and Bernards, 2014) and histology agnostic clinical trials (Lacombe et al., 2014). These publications are adding further information and reading is recommended. We hope that this issue will achieve its educational mission and stimulate interest in further development of clinical trials methodology. Success will require new types of collaborations between clinical cancer researchers and the biotechnology/pharmaceutical industry. The next generation of clinical trials will need these collaborations in order to reach the critical mass of patients required for trials on small, biomarker-selected subpopulations. The initiative for this issue of Molecular Oncology came from the EU-funded EurocanPlatform project, which initiated collaborations between cancer research centres in translational cancer research. The newly formed Cancer Core Europe, a consortium of six European centres, and the WIN consortium, a worldwide clinical research collaboration, are examples of joint efforts aimed at reaching a critical mass of patients required for innovative clinical trials in personalized cancer medicine.