Proposals under this topic should aim to deliver results that are directed and tailored towards, and to contribute to all of the following expected outcomes:

• Researchers and health professionals understand tumour-host processes that spur cancer development and progression in patients and how this forms the basis for the future design and optimisation of treatment or care interventions for poorly-understood cancers and their subtypes, including in children, adolescents, adults and the elderly.
• Researchers, innovators, and professionals from different disciplines and sectors ensure accessibility and re-usability of their data, models, tools and technology to support the UNCAN.eu^[1] platform, which is currently in preparation.
• Health policy makers are aware of an improved understanding of tumour-host interactions in cancer patients that would allow the co-design of cancer-related innovation and health policies in the Member States, Associated Countries and beyond, including those aimed at delivering treatment and care developing care solutions for and with cancer patients.

This topic will contribute to the achievement of the Mission’s objective to better understand cancer by studying tumour-host interactions underpinning the development and progression of cancer, including in advanced localised or metastatic disease. The focus should be on poorly-understood^[2] cancers and their subtypes in children, adolescents, adults and the elderly.

Despite important progress and recent successes with, for example immune system-centred therapeutic interventions^[3] understanding of tumour-host interactions in cancer patients remains incomplete. Challenges include uncovering which patients benefit from interventions or risk potentially debilitating side-effects, as well as ensuring affordability of interventions across Europe, across all age groups. This requires a new dimension and level of investment in innovative research with a view to intercept disease. It also requires investing in high-risk, high-reward research projects to deliver a proof-of-concept of potentially disruptive new approaches. These approaches include monitoring treatment and disease progression and disclosing disease pathways, such as through single-cell -omics technologies, innovative disease models, advanced imaging technologies, or artificial intelligence and machine learning.

Proposals should address all of the following:

• Obtain a systematic understanding of processes underpinning tumour-host interactions in poorly-understood cancers and their subtypes in childhood, adolescent, adult and elderly cancer patients. Applicants should take into account social, ethnical, cultural and gender aspects, with a focus on the transition from a healthy state to cancer initiation and progression, including in advanced localised or metastatic disease (where relevant), using any relevant in silico, in vitro, in vivo, ex vivo, preclinical, or clinical disease models as well as computational, simulation and visualisation tools and technologies where appropriate.
• Combine knowledge and high-quality data from biomedical and clinical studies, and real-world data, using advanced digital tools and technologies such as computer modelling and artificial intelligence with the objective to understand relevant tumour-host interactions and their impact on treatment and care solutions for cancer patients.
• Demonstrate access to and use of multiple comprehensive databases in and beyond health research or health domains. Proposals should build on longitudinal clinically annotated, stratified patient cohorts, case-control studies, biobanks, registries and many other initiatives^[4], use state-of-the art digital and other tools for data analyses and modelling, wherever possible.
• Based on results obtained, propose socially acceptable, affordable novel treatment or care interventions or health technologies for uptake into health systems in the areas of treatment or care, using approaches that involve the end-user using participative research models.

This topic requires the effective contribution of SSH disciplines and the involvement of SSH experts, institutions as well as the inclusion of relevant SSH expertise, in order to produce meaningful and significant effects enhancing the societal impact of the related research activities.

Due consideration should be given to EU-funded initiatives such as: HealthyCloud^[5], EOSC-Life^[6], the Photonics21 partnership – including its Photon Hub Europe support service^[7], the Innovative Health Initiative partnership^[8], the European Health Data Space (EHDS) Joint Action^[9], 1+ Million Genomes (1+MG)^[10] / Beyond One Million Genomes (B1MG)^[11], the EBrains^[12] research infrastructure and the EIT Health Knowledge Innovation Community initiatives^[13]. Links with the research infrastructure projects EOSC4cancer^[14] and canSERV^[15], as well as projects funded by other EU programmes^[16] are encouraged.

Successful applicants will be asked to liaise with these and other initiatives where applicable^[17]. The successful proposals are expected to liaise with and build on resources made available by the Knowledge Centre on Cancer (KCC)^[18] in order to foster EU alignment and coordination.

The Commission will facilitate Mission-specific coordination through future actions, notably fostering exchanges with other proposals funded under this topic. Hence, successful applicants will be asked to join the 'Understanding' cluster for the Mission on Cancer established in 2022^[19]. In this regard, the Commission will take on the role of facilitator, including with relevant initiatives and stakeholders, if appropriate.

Therefore, proposals should include a budget for networking, attendance at meetings, and potential joint activities without the prerequisite to give details of these at this stage. Examples of these activities are the organisation of joint workshops, the exchange of knowledge, the establishment of best practices, or the initiation of joint communication activities with projects funded under other clusters and pillars of Horizon Europe, or other EU programmes, as appropriate. The details of joint activities will be defined during the grant agreement preparation phase and during the life of the project.

[1] Under the Mission work programme a Europe-wide research and data platform, UNCAN.eu, will be established, utilising existing, relevant research infrastructures. Once operational, the platform should enable integration of innovative models and technologies with longitudinal patient data, data beyong research, or the health domain, samples and biomarkers for translation to patients. The 4.UNCAN.eu project is preparing a blueprint. See: https://cordis.europa.eu/project/id/101069496)

[2] Includes refractory cancers and their subtypes, at any stage of the disease in any age group and part of society, with a 5-year overall survival less than 50% from time of diagnosis.

[3] Such as cell-based and oncolytic viral therapy, therapeutic antibodies, therapeutic DNA, RNA and peptide vaccines; and multimodal interventions combining surgery, chemotherapy, and radiotherapy with immune system-centred interventions

[4] Many retrospective, prospective cohorts, case-control studies and initiatives -in health and well-beyond health- at local, regional, national, European and international level, exist.

[5] https://healthycloud.eu/

[6] https://www.eosc-life.eu

[7] https://www.photonics21.org/index.php; Photon Hub Europe: https://www.photonhub.eu

[8] https://www.ihi.europa.eu/

[9] https://tehdas.eu/

[10] https://digital-strategy.ec.europa.eu/en/policies/1-million-genomes

[11] https://b1mg-project.eu/

[12] https://ebrains.eu/

[13] https://eithealth.eu/who-we-are/

[14] https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/how-to-participate/org-details/999999999/project/101058427/program/43108390/details

[15] https://cordis.europa.eu/project/id/101058620

[16] E.g. pilot projects on artificial intelligence for diagnosis and treatment of paediatric cancer selected for funding from the calls PPPA-AIPC-2020 and PPPA-AIPC-2021; Joint Action “JANE” under the EU4Health programme (“Network of Comprehensive Cancer Centres: Establishment of new EU Network of Expertise on Cancers and Cancer Conditions”).

[17] Applicants are not expected to contact these initiatives before the submission of proposals.

[18] Hosted by the European Commission's Joint Research Centre (JRC). Especially through the ’European Guidelines and Quality Assurance Schemes for Breast, Colorectal and Cervical Cancer Screening and Diagnosis‘, and the ’European Cancer Information System (ECIS)’ and the ’European Cancer Inequalities Registry (ECIR), see https://knowledge4policy.ec.europa.eu/cancer_en

[19] In order to address the objectives of the Mission on Cancer, participants will collaborate in project clusters to leverage EU-funding, increase networking across sectors and disciplines, and establish a portfolio of Cancer Mission R&I and policy actions.