Tumors are complex and dynamic tissues encompassing both transformed cancer cells and a variety of genetically normal but metabolically corrupted host cells, which include fibroblasts, vascular cells, and a diverse assortment of immune cells. Cancer and host cells, along with the extracellular matrix they are embedded in, are collectively referred to as the “tumor microenvironment” (TME). The complexity of the TME is such that tumor development and response to therapy are markedly influenced by its composition and the multidimensional cross talk between cancer cells and host cells, which vary with the tumor stage, organ site, and therapeutic regimen used. Importantly, several host components of the TME represent actionable anti-cancer targets. The key goals of researchers at the AGORA cancer research center are to better understand how the evolving TME orchestrates tumor progression and to identify new vulnerabilities in the TME that could improve the efficacy of anti-cancer therapies.

Imaging has become an indispensable tool in medical practice, for example to allow physicians to locate a tumor, to define its biological activity, and to know whether it is controlled by a given treatment. Imaging technologies are also essential in experimental cancer research, as they allow the observation of cellular behaviors and molecular signals deep within tissues, and thus provide quantitative and dynamic information about tumor biology. For example, intravital imaging has become useful for interrogating components of the tumor microenvironment in a spatiotemporal manner. Some of the objectives of researchers at the AGORA cancer research center are to use cancer imaging to understand the activity of tumor cells, immune cells and drugs, in tissue microenvironments. These approaches allow us to discover the cellular and molecular mechanisms that promote or control tumor progression, and to better understand how a treatment works (or fails) and can be improved.

Bioengineering approaches have opened many new avenues in cancer research, particularly when being exploited in an interdisciplinary way. For example, the combination of microfluidics, novel sequencing technologies and computational analyses has been crucial to enable single cell assays, giving a detailed picture of tumor heterogeneity for the very first time. In a similar way, progress on the technology and instrumentation side has been elementary for generating large data sets in multidimensional cancer “omics” approaches, cell-cell interaction screens, 3D tumor models and tissue level analyses. Researchers at the AGORA cancer research center are very active in these domains, with the overarching goals of: gaining a deeper insight into disease mechanisms, identifying new drug targets and biomarkers, screening immune repertoires for cells and antibodies with therapeutic potential, and developing personalized therapy approaches.

In recent years, immunotherapy has been an exciting new development in the systemic treatment of cancer. Immunotherapy can stimulate or alter the functioning of the immune system so that it can find and attack cancer cells. This includes the mechanisms by which tumours counter the immune attack and the development of new immunotherapies. By integrating basic, translational and clinical research, researchers at the AGORA cancer research center aim to better understand the relationship between the immune system and cancer in order to develop personalised immunotherapy treatments. The focus is on immunotherapies tailored to each patient’s cancer, such as dendritic cell-based vaccines and therapies that involve the engineering and reincorporation of the patient’s own T cells (CAR-T cell therapy). In collaboration with the partner hospitals, the aim is to develop technologies to standardise and streamline these personalised therapies, which will be essential for their wider deployment.

The overarching goal of Precision Oncology is to tailor specific treatments to specific patients by taking into account everything that is known about them, including their demographics, clinical history, genome, proteome, disease physiology, and more. While this notion of personalized care places the focus on one target patient, the corollary is that prior information about a huge number of similar patients is needed to enable statistically significant inferences. Hence precision oncology relies on the availability of data, which can be generated through targeted clinical trials, translational experiments, or through retrospective analysis of real-world data generated in standard clinical practice. Based on this, cutting-edge data analytics enable: (i) Finding patients with similar profiles and diagnoses to discover prognostic biomarkers of disease evolution; (ii) Comparing responses to different treatments in groups of patients with homogeneous profiles to discover predictive biomarkers of treatment outcome; (iii) Generating hypotheses on the biological mechanisms underlying disease and treatment action, which can be subsequently validated in research settings.

Metastasis is a multi-step, complex evolutionary process by which some cancer cells break away from their original tumour and spread to distant organs. Each stage of metastasis adds considerable heterogeneity to the tumour and includes the acquisition of stem cell characteristics. These cancer stem cell populations have distinct molecular, genetic and phenotypic characteristics, which together increase the risk of treatment resistance. Indeed, cancer metastasis is the leading cause of death in the majority of solid cancers. Some of the objectives of the researchers at the AGORA cancer research center are to understand the early events of metastatic initiation and growth, the mechanisms involved in cancer dissemination, with a focus on interactions with the microenvironment at several stages of the metastatic cascade, cell regulation and cancer stem cells. These approaches allow us to analyse each step of molecular and cellular changes during the metastatic process and thereby identify new implications for the clinic.