Dr. Alexandra Boitor, EACR Scientific Officer, writes about her experience and scientific highlights from the EACR Conference ‘Goodbye Flat Biology’, which was held in Berlin, Germany from 10-12 October 2023.

Traditionally, the EACR Goodbye Flat Biology conferences focus on the next generation of cancer models that more accurately reflect the biochemical, spatial, and mechanical properties of tumours in their tissue environment. This year was no exception and talks at the conference covered a range of novel technical approaches to modelling cancer.

From modelling tumours to understanding cell invasion and metastasis

The conference featured a series of talks discussing cell invasion and metastasis. Renowned scientists such as Dr Andrew Ewald (USA), Dr Laura Machesky (UK), Dr Peter Friedl (NL), and Dr Jacky Goetz (FR) presented their latest research on this topic and discussed the benefits and shortcomings of different types of cell invasion. The importance of epithelial-to-mesenchymal transition, cell polarity, metabolic needs of the cell and the impact of the tumour microenvironment were addressed in the context of cell mobility, invasion and ability to metastasise, and signalling pathways that regulate these processes were analysed.

For instance, in his presentation, Dr Andrew Ewald discussed the role of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (TME) in metastasis formation in triple-negative breast cancer. Dr Ewald’s research reveals the existence of several hybrid epithelial-mesenchymal states characterised by simultaneous expression of both epithelial and mesenchymal markers in different proportions. Single-cell analysis of TNBC metastatic samples revealed heterogeneity of epithelial/ mesenchymal states within the same tumour [1]. In his presentation, Dr Ewald also discussed the broader role that E-cadherin plays in metastasis formation in invasive ductal carcinoma beyond EMT and cell invasion, highlighting a role for E-cadherin in mitigating response to oxidative stress, modulating survival of invasive cells and determining their metastatic potential [2].

Whilst Dr Ewalds’s talk highlighted the advantages of collective cell invasion over disseminative invasion, Dr Peter Friedl discussed the transition from collective cell invasion to ameboid movement. Dr Friedl’s research looked at how malignant cells adapt their invasion modes in response to microenvironment constraints, more exactly how hypoxia determines cells to switch to an ameboid-type movement to preserve energy [3].

In her presentation, Dr Laura Machesky looked at how cancer cells “decide when to eat and when to walk”, with a focus on micropinocytosis. In her research, Dr Machesky looked at how CYRI-A and CYRI-B regulate micropinocytosis, integrin trafficking, actin dynamics and chemotactic potential and the impact they have on apicobasal polarity, cell invasion and metastasis, especially in pancreatic cancer [4, 5].

The conference took place at Harnack House in Berlin

From modelling tumours to improving cancer treatment

Another popular topic was modelling the tumour and its microenvironment to improve drug discovery, and to understand therapy resistance. Henriëtte Lanz (NL), Erik Sahai (UK), Paul Timpson (AU), Silvia Scaglione (IT) and Valerie Weaver (USA) ‘s recent research addressed the questions of how the tumour microenvironment, intra-tumoral heterogeneity and processes such as angiogenesis, hypoxia and apoptosis modulate tumour response to treatment, but also how these processes are regulated at an epigenetic level.

For instance, in her presentation, Dr Valerie Weaver highlighted the potential that patient-derived organoids hold for treatment development and new drug discovery. By studying organoids derived from tumours from chemotherapy-treated breast cancer patients, Dr Weaver identified NCOR2 as a predictor of recalcitrant tumours. By regulating HDAC3, NCOR2 modulates interferon signalling hence controlling cytotoxic stress response and antitumor immunity [6].

By using a mixture of PDAC models from classical 2D cell cultures to 3D cell cultures and patient-derived xenografts combined with intra-vital imaging Dr Paul Timpson investigated the potential of combining FAK inhibition with standard-of-care chemotherapy to improve treatment response. In his presentation, Dr Timpson shows that FAK priming modulates cell-matrix stiffness, reducing the invasive and metastatic potential of tumour cells whilst sensitising them to chemotherapy [7].

EACR conferences include dedicated poster discussion sessions for networking

A few examples of technological advances presented at Goodbye Flat Biology

From a technical perspective, talks and posters at the Goodbye Flat Biology conference presented complex 3D cultures, various organoid models, ECM-derived hydrogels, organ-on-a-chip approaches, ex-vivo avatars, co-cultures and biometric models of tumour vasculature that capture the dialogue between cancer cells, the cellular stroma, and the extracellular matrix.

In her talk, Dr Silvia Scaglione presented a new organ-on-chip approach capable of mimicking NK cell tumour infiltration under physiological fluid flow conditions. This model consists of two compartments separated by a porous permeable membrane. The upper chamber allows for 3D tumour culture whilst in the lower chamber cultured NK cells are circulated under conditions mimicking the blood flow velocity in capillaries. This allows NK cells to migrate to the tumour upwards (anti-gravity) and against viscous forces, making this system more physiologically relevant and thus promising for testing immunotherapies [8].

Dr Anne Rios (NL) also presented an in vitro model designed to study the immune cell-tumour interactions. This system, BEHAV3D, relies on single-cell imaging and transcriptomic profiling, allowing for the life-tracking of engineered T-cells co-cultured with patient-derived organoids. This system allows for the identification of new T-cell behaviours and the detection of behaviour-specific gene signatures, as exemplified by Dr Rios for the ‘super-engager’ T-cells [9].

In addition to the incredibly interesting scientific talks, the conference benefited from a fascinating poster display that sparked vivid discussions. The conference also featured a highly valued meet-the-expert session where Andrew Ewald shared his own personal and professional experiences of his path to scientific leadership and offered advice to early-career researchers present at the conference.  

The meeting was highly regarded by its participants both for the scientific excellence and for the networking opportunities. The presented data and newly acquired knowledge will serve participants to improve their own research activities. This meeting was regarded as being particularly useful for developing collaborations with peers to advance the development of in vitro and ex vivo cancer models that are more representative of the disease. 

EACR Conferences

At the EACR we are dedicated to providing excellent cancer research conferences where the latest research topics and interaction for participants are the very highest priorities. Make sure you add the dates of the upcoming EACR Conferences to your diary now. Don’t forget we offer member discounts on all of our registration fees!

References

  1. Grasset, E.M., et al., Triple-negative breast cancer metastasis involves complex epithelial-mesenchymal transition dynamics and requires vimentin. Science Translational Medicine. 14(656): p. eabn7571.
  2. Padmanaban, V., et al., E-cadherin is required for metastasis in multiple models of breast cancer. Nature, 2019. 573(7774): p. 439-444.
  3. te Boekhorst, V., et al., Calpain-2 regulates hypoxia/HIF-induced plasticity toward amoeboid cancer cell migration and metastasis. Current Biology, 2022. 32(2): p. 412-427.e8.
  4. Le, A.H., et al., CYRI-A limits invasive migration through macropinosome formation and integrin uptake regulation. Journal of Cell Biology, 2021. 220(9): p. e202012114.
  5. Nikolaou, S., et al., CYRI-B mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. bioRxiv, 2022: p. 2022.11. 23.517689.
  6. Tsai, K.K., et al., Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity. Nature Cancer, 2022. 3(6): p. 734-752.
  7. Murphy, K.J., et al., Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status. Science Advances, 2021. 7(40): p. eabh0363.
  8. Marzagalli, M., et al., A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model. Frontiers in Bioengineering and Biotechnology, 2022. 10: p. 945149.
  9. Dekkers, J.F., et al., Uncovering the mode of action of engineered T cells in patient cancer organoids. Nature Biotechnology, 2023. 41(1): p. 60-69.

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