The EACR conference on Cancer Genomics, widely recognised as the premier European conference dedicated to this topic, evolved its content in 2024 to cover the latest exciting developments in machine learning and artificial intelligence, single cell and spatial analysis of cancers, cell plasticity, cancer immune genomics, data integration and convergence, epigenetics, and genomic instability.
The EACR conference on Cancer Genomics, Multiomics and Computational Biology was held between 30 April – 2 May 2024 in Bergamo, Italy and brought together 236 delegates from 32 countries, including 15 renowned invited speakers from some of the biggest research institutes in Europe, the US and Canada, 8 proffered papers selected from the submitted abstracts, and 128 posters, including 6 Poster Spotlights. Dr. Alexandra Boitor, EACR Scientific Officer, summarises here the main scientific takeaways from this meeting.
Featuring an exceptional international faculty and extensive networking opportunities, this EACR conference aimed to explore genomic, transcriptomic, and epigenetic changes that underpin cancer evolution and immune evasion. The conversation focused not only on machine learning and artificial intelligence approaches to analyse and integrate multiomic data and identify the (neo)antigenic landscape and specific antitumor T-cell response in human cancers, but also highlighted multiple uses of single-cell sequencing from cell tracking to monitor evolution and plasticity to spatial and 3D analysis of tumours at molecularly annotated single-cell resolution.
The conference started with an opening keynote by Julian Downward who discussed how the clinical impact of anti-KRAS therapies could be improved by modulating the anti-tumor immune response. Prof Downward’s presentation focused on K-RAS driven lung cancer and started by highlighting the shortcomings of current MEK inhibitors on RAS mutant cancers from insufficient target inhibition to failure to target multiple effectors with overlapping functions on the MAPK pathway, from signalling pathway adaptation due to loss of negative feedback to the lack of therapeutic window, from tumour heterogeneity to the loss of oncogene addiction, leading to reduced clinical utility due to high toxicity and the rapid emergence of drug resistance [1].
Prof Downward’s lab focused on investigating the impact of the RAS mutations and treatment with KRAS inhibitors on the tumour microenvironment in lung cancer, especially on the ability of RAS mutant tumour cells to contribute to an immunosuppressive tumour microenvironment [2, 3]. This provided a rationale for combining RAS inhibitory drugs with anti-PD-1 treatment, a promising approach in most immunogenic tumours, and combining targeting of Tregs along with KRAS in immune cold tumours [3].
Some other outstanding talks were those by Elaine Mardis on the progress made in clinical trials with oncolytic viral therapy immunogenomics in adult glioblastoma [4] and Elisa Oricchio on the modulation of 3D chromatin structures to support tumour evolution [5] just to name a few. From a technological perspective, the single-molecule and single-cell epigenetic technologies developed by Efrat Shema’s lab stood out. Dr Shema provided an update on the progress her lab made since the 2022 EACR conference on Liquid Biopsies in developing the EPINUC technique, a single-cell imaging technique of the epigenetic code in plasma-isolated nucleosomes and its potential clinical application for the detection and monitoring of plasma circulating nucleosomes and oncoproteins in Diffuse Midline Glioma [6].
The conference concluded with the EMBO keynote lecture given by Nuria Lopez-Bigas who discussed how the clonal selection occurring in the normal tissues relates to cancer risk. In her talk, Dr Bigas highlighted that cancer driver mutations are often present in healthy tissue suggesting they might not be enough on their own to drive tumorigenesis. Dr Bigas proposes the need for a ‘promotion step’ in the process of tumour formation that would provide a growth advantage to the cells harbouring such mutations. In order to explore the effect that carcinogens have on healthy tissue, Dr Bigas investigates how chemotherapy can provide a selective advantage to preexisting mutations [7-9].
The EACR conference on Cancer Genomics, Multiomics and Computational Biology covered the latest exciting breakthroughs in multiple aspects of cancer genomics and multiomics, including novel technologies and computational approaches. The scientific presentations at this conference touched on several ‘hot’ topics in the cancer research field including immunooncology, response to therapy, liquid biopsies and tumour microenvironment. In addition to the exciting science, the conference also featured various networking opportunities, including a ‘Meet the Scientific Programme Committee’ session where the committee members reflected on the conference and invited feedback before each providing insight into their personal and professional experiences of their routes into scientific leadership.
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References:
- Molina-Arcas, M. and J. Downward, Exploiting the therapeutic implications of KRAS inhibition on tumor immunity. Cancer Cell, 2024. 42(3): p. 338-357.
- Enfield, K.S.S., et al., Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer. Cancer Discov, 2024. 14(6): p. 1018-1047.
- Cole, M., et al., Spatial proteomic analysis of a lung cancer model reveals regulatory T cells attenuate KRAS-G12C inhibitor-induced immune responses. bioRxiv, 2024: p. 2024.04.11.588725.
- Miller, K.E., et al., Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study. Clinical Cancer Research, 2022. 28(3): p. 498-506.
- Lambuta, R.A., et al., Whole-genome doubling drives oncogenic loss of chromatin segregation. Nature, 2023. 615(7954): p. 925-933.
- Erez, N., et al., Single-molecule systems for detection and monitoring of plasma circulating nucleosomes and oncoproteins in Diffuse Midline Glioma. bioRxiv, 2023: p. 2023.11.21.568019.
- Sánchez-Guixé, M., et al., Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues. Cancer Discovery, 2024. 14(6): p. 953-964.
- Pich, O., et al., The evolution of hematopoietic cells under cancer therapy. Nature Communications, 2021. 12(1): p. 4803.
- Pich, O., et al., The mutational footprints of cancer therapies. Nat Genet, 2019. 51(12): p. 1732-1740.
