Skip to content
What's on

Forces in cancer: interdisciplinary approaches in tumour mechanobiology

Discussion meeting

Starts:

June
182018

09:00

Ends:

June
192018

17:00

Location

The Royal Society, London, 6-9 Carlton House Terrace, London, SW1Y 5AG

Overview

Scientific discussion meeting organised by Dr Chris Bakal and Dr Julia Sero

Melanoma cell spreading on collagen matrix. Credit: Chris Bakal and Oliver Inge

In the last decade, research from diverse fields has converged to establish a fundamental concept: that physical forces play key roles in both the initiation and progression of cancer. This meeting will bring together an interdisciplinary group of pioneering scientists tackling cancer mechanobiology from many angles to present the latest developments in the field.

The speaker biographies and talk abstracts are available below. Recorded audio of the presentations will be available on this page after the meeting has taken place. Meeting papers will be published in a future issue of Philosophical Transactions B.

Enquiries: Contact the Scientific Programmes team.

Event organisers

Select an organiser for more information

Schedule of talks

18 June

09:00-12:00

From D’Arcy Thompson to cancer mechanobiology

6 talks Show detail Hide detail

Chairs

Dr Chris Bakal, Institute of Cancer Research, UK

09:00-09:30 Opening talk and introduction to the meeting

09:30-10:00 Cell morphogenesis across scales, from molecular processes to cell shape control

Professor Ewa Paluch, MRC-LMCB, University College London, and PDN, University of Cambridge, UK

Abstract

A precise control of cell morphology is key for cell physiology, and cell shape deregulation is at the heart of pathological disorders, such as cancer. Cell morphology is intrinsically controlled by mechanical forces acting on the cell surface, to understand shape it is thus essential to investigate the regulation of cellular mechanics. In animal cells, shape is primarily determined by the cellular cortex, a thin network of actin filaments and myosin motors underlying the plasma membrane. The Paluch lab investigates how the mechanical properties of the cell surface arise from the microscopic organisation of the cortex, and how changes in these properties drive cell deformation. This talk will present methods to investigate cortex composition and nanoscale architecture, and discuss how cortical network mechanics are regulated. Using a combination of cell biology experiments, quantitative imaging and physical modelling, the aim is to understand the control of cell shape across scales.

Show speakers

10:00-10:30 Mechanotransduction: from the cell surface to the nucleus

Professor Keith Burridge, University of North Carolina, USA

Abstract

Mechanical forces affect many aspects of normal and tumour cell behaviour. To explore the physical role of the nucleus in mechanotransduction, nuclear-cytoskeletal connections were severed or cells were enucleated generating “cytoplasts”. The nucleus was not required for the establishment of cell polarity, migration in 1D or 2D, for chemotaxis or haptotaxis. However, cytoplasts were defective in migrating in 3D matrices. By several assays, cytoplasts exerted less force on the extracellular matrix and revealed decreased RhoA activity. Increasing substratum rigidity elevates RhoA activity. This has previously been attributed to Rho GEF activation downstream from integrins responding to actomyosin generated mechanical tension. However, the role of Rho GAPs has not been investigated in this pathway. In response to increasingly rigid substrata decreased p190RhoGAP activity was observed contributing to the overall activation of RhoA. Exploring the pathway involved revealed decreased expression of Rnd3/RhoE on rigid substrata. Rnd3 is a constitutively active Rho family member that antagonizes RhoA by activating p190RhoGAP. Driving Rnd3 expression stimulated p190RhoGAP and decreased RhoA activity.

Show speakers

10:30-11:00 Coffee break

11:00-11:30 Mechanisms underlying force-induced invasive migration of cancer cells

Professor Benny Geiger, Weizmann Institute of Science, Israel

Abstract

In this talk, three inter-related mechanisms underlying invasive migration of cancer cells are discussed. (1) A non-canonical form of invasive collective migration, displayed by the metastatic murine mammary carcinoma cell line 4T1. Benjamin Geiger shows that in sparsely plated cells, E-cadherin levels are reduced by ~50%, leading to a loose collective migration of the cells, that are interconnected by thin membrane tethers. Interestingly, knocking down E-cadherin by over 90% prevented tether formation in these cells, and greatly enhanced their individual migratory rate. Nevertheless, despite their enhanced migration the knocked-down cells became poorly metastatic and displayed reduced invasive properties ex vivo. These findings suggest that the moderate E-cadherin levels, present in wild-type 4T1 cells, play a key role in promoting cancer invasion and metastasis. The mechanism underlying this effect is discussed. (2) Environmental induction of cell invasion is also demonstrated in studies showing that breast carcinoma BT-474, exposed to specific populations of stromal fibroblasts, become highly invasive, and penetrate into the stromal monolayer. A search for the molecular basis of this invasion induction, identified a specific combination of two cytokines, namely IL1 and IL6, which can be secreted by different sub-populations of stromal cells, as the invasion promoting components. The cross-talk between these cytokines and their cooperation in inducing invasive EMT are discussed. (3) Invadopodia-mediated invasion. Invadopodia are actin-rich protrusions of the plasma membrane that attach to, penetrate into the extracellular matrix and induce its degradation. Invadopodia are commonly formed by cancer cells and are believed to promote tumour invasion and metastasis. In this study the functional bio-mechanics of invadopodia in cultured A375 melanoma cells, were investigated, using a combination of correlative microscopy approaches. This study demonstrated that the core actin bundle of invadopodia tend to form “under” the nucleus and to push against the nucleus and actually indent it. Estimation of the forces applied to the nucleus by the underlying invadopodia, based on the indentation profile and the viscoelastic properties of the nucleus, suggest that the pushing forces applied by the actin bundle to both the nucleus and to the matrix are in the ~20 nN/µm2 range. This cytoskeletal protrusion, combined with the adhesion to the matrix and the local matrix degradation activity are believed to contribute to the initial stages of the invasive process.

Show speakers

11:30-12:00 Extrinsic and intrinsic force regulates cancer progression, aggression and treatment

Professor Valerie Weaver, University of California, San Francisco, USA

Abstract

All cells experience force and possess mechanosensory mechanisms that enable them to detect mechanical stimuli and transduce these cues into biochemical signals that modify protein function and alter gene expression to influence cellular behaviour. Tumours have higher cell and tissue level forces and transformed cells exhibit perturbed mechanosensing. Valerie Weaver’s group has been studying the genesis of the altered tumour cell and tissue force and how cells sense and transduce mechanical cues to drive tumour formation and aggression and treatment response. Using an array of in vitro and in vivo models they found that the ECM progressively stiffens in peripheral tumours such as the breast, skin and pancreas mediated largely by increased collagen deposition, remodelling and crosslinking and induction of fibrosis. Even in tumours such as glioblastomas which do not exhibit fibrosis the ECM stiffens due to enhanced hyaluronic acid deposition and proteoglycan crosslinking. The Weaver group uniformly finds that a stiffened tumour ECM enhances integrin signalling to promote malignant transformation and tumour aggression that ultimately compromises treatment responsiveness. Consistently, inducing ECM tension or increasing integrin signalling promotes the malignant transformation of premalignant oncogenically-primed cells and drives the aggressiveness of tumours, whereas inhibiting ECM stiffening prevents tumour progression and reduces aggression. Importantly, when tumour cells are oncogenically transformed or loose expression of critical tumour suppressors they show a significant increase in actomyosin tension and enhanced integrin focal adhesion and growth factor receptor signalling. The high tumour cell tension fosters tumour progression and aggression in part by stiffening and remodelling the ECM. The stiff ECM also compromises the tissue vasculature to induce hypoxia and HIF1a to promote a mesenchymal-like phenotype that is highly resistant to therapy. The stiff ECM also modulates tumour immunity and regulates levels of key repressors that modulate anti-tumour cytotoxic responsiveness.

Show speakers

12:00-13:00

Lunch

13:00-17:00

Mapping and targeting mechanotransduction networks in cancer

8 talks Show detail Hide detail

Chairs

Dr Julia Sero, Institute of Cancer Research, UK

13:00-13:15 Introduction to session talk

13:15-14:15 Tissue regeneration, stem cells and cancer: roles of the mechanotransducers YAP/TAZ

Stefano Piccolo, Padua University, Italy

Abstract

Stefano Piccolo studies how cells sense their environment and use this information to build and maintain tissues with specific form, size and function, and how these systems are corrupted in diseases. At the centerpiece of these events is the activity of the transcriptional coactivators YAP and TAZ. Enhanced YAP/TAZ activity is emerging as a hallmark of multiple human tumours. Stefano will discuss the cell and tissue-level mechanisms that lead to unrestrained YAP/TAZ activity, in turn essential for tumour formation and for tissue regeneration upon injury. He will also present new evidence on the function of YAP/TAZ in regulating the biology of normal somatic stem cell explanted from adult tissues.

Show speakers

13:45-14:15 CDK1 inhibition is the trigger for remodelling of adhesion complexes in G2 phase of the cell cycle

Professor Martin Humphries FMedSci, University of Manchester, UK

Abstract

In most tissues, anchorage-dependent growth and cell cycle progression are dependent on the engagement of cells with extracellular matrices via integrin receptor adhesion complexes. In a highly conserved manner, cells disassemble adhesion complexes, round up, and retract from their surroundings prior to division, suggestive of a primordial link between the cell cycle machinery and the regulation of cell-extracellular matrix adhesion. In this talk, Martin Humphries demonstrates that CDK1, a promiscuous serine/threonine kinase and master regulator of the cell cycle, mediates this link. CDK1, in complex with cyclin A2, has an interphase role in promoting adhesion complex and actin cytoskeleton organisation, and it also mediates a large increase in adhesion complex area as cells transition from G1 into S. Adhesion complex area starts to decrease early in G2 and disassembly occurs several hours prior to mitosis. This loss requires elevated cyclin B1 levels and is caused by inhibitory phosphorylation of CDK1-cyclin complexes. The inactivation of CDK1, which prevents phosphorylation of its myriad substrates, is therefore the trigger that initiates remodelling of adhesion complexes and the actin cytoskeleton in preparation for rapid entry into mitosis.

Show speakers

14:15-14:45 The dark side of fibroblast force

Dr Danijela Matic Vignjevic, Institute Curie, France

Abstract

Tumour microenvironment plays an important role in the tumour progression. It is made of extracellular matrix (ECM), blood vessels, immune cells and cancer-associated fibroblasts (CAFs). Besides biochemical signals, mechanical forces from microenvironment also play a role in tumour progression. CAFs have enhanced contractility and capacity to synthesize, deposit and crosslink ECM making stroma stiffer. Thus, by accumulating around the tumour, they could provide a physical barrier constraining tumour expansion. However, it has been shown that by exerting mechanical forces on the ECM, CAFs also enhance tumour invasion. These antagonistic roles of forces produced by CAFs in tumour progression will be discussed.

Show speakers

14:45-15:15 Tea break

15:15-15:45 Endocytic control of mechanics, collective motion and cancer progression

Dr Giorgio Scita, IFOM, FIRC Institute of Molecular Oncology, Italy

Abstract

Collective motility is ruled by both biochemical and physical interactions that cells establish among each other and with their environment. An emerging framework to interpret these interactions in unifying principles is the notion of cell jamming. During collective motility cells can flow like a fluid, but as density rises, the motion of each cell is constrained by the crowding due to its neighbours. At a critical density, motility ceases and collectives rigidify undergoing a liquid (unjammed)-to-solid (jammed) transition, herein referred to as UJT. This transition is thought to ensure proper development of barrier properties in epithelial tissues, but also to act as a tumour suppressive mechanism. The reverse, JUT might, instead, represent an alternative gateway to cell migration, enabling tissues to escape the caging imposed by the crowded cellular landscape of mature epithelia. The general validity of this physical framework and of JUT, however, remains to be verified. Even less understood is how cells control such phase transitions. In this talk, Giorgio Scita will address these issues and discuss whether the transition between “solid” and “liquid” locomotory states is an alternative or complementary gateway to epithelial-to-mesenchymal transition (EMT) to account for the plastic remodelling of epithelial tissues in physiology and pathology.

Show speakers

15:45-16:15 Cell collision geometry is critical for the emergence of extracellular matrix anisotropy

Dr Erik Sahai, Francis Crick Institute, London, UK

Abstract

The organisation of the extra-cellular matrix (ECM) is crucial in determining both tissue structure and function. Many matrix proteins are organised into fibrillar structures with diameters in the range of 10-100nm and lengths in the range 10-100μm. Higher levels of organisation extending into the millimetre scale are also observed with aligned anisotropic matrices found in many tissues and pathologies, such as cancer and fibrosis. How such aligned ECM is generated is not well understood. Erik Sahai has undertaken a comprehensive survey of fibroblastic cells comparing those that generate highly aligned anisotropic matrices with those that don’t. His group has found that higher order alignment enables the coordination of traction forces and thereby millimetre scale collagen re-organisation. Detailed analysis of the emergence of aligned matrices reveals an unexpected role for cell collisions in coordinating ECM geometry. Further, combined RNAseq analysis reveals the transcriptional regulatory network that enable this behaviour.

Show speakers

16:15-17:00 Summary

Dr Chris Bakal, Institute of Cancer Research, UK
Dr Julia Sero, Institute of Cancer Research, UK

Show speakers

19 June

09:00-12:00

Imaging morphology, migration and metastasis

6 talks Show detail Hide detail

09:00-09:30 Plasticity of cancer cell invasion and metastasis

Dr Peter Friedl, Radboud University Nijmegen Medical Centre, The Netherlands, and The University of Texas, MD Anderson Cancer Center, USA

Abstract

Cancer cell migration is a plastic and adaptive process generating molecular and physical heterogeneity of migration mechanisms and metastatic routes, including single-cell and collective metastasis. When monitored in vivo using intravital multiphoton microscopy, tissue microniches provide invasion-promoting tracks that enable collective migration along tracks of least resistance. In regions of tissue confinement, invading cancer cells undergo a jamming transition towards collective migration and circulate as both individual cells and multicellular clusters for collective organ colonisation. Using multi-targeted interference with integrin adhesion systems, conversion from collective invasion to amoeboid single-cell dissemination followed by increased rates of lung colonisation was detected. Similar amoeboid dissemination was induced by hypoxia or stabilisation of hypoxia-inducible factor (HIF). The data suggest that metastatic cancer cells can undergo physicochemical reprogramming in response to encountered tissue environments, and thereby balance cell-intrinsic adhesion and mechanocoupling with encountered cues. Dissecting the microenvironmental determinants underlying individual-to-collective plasticity, and vice versa, will enhance to derive combined “antimigration” and cytotoxic therapies and combat metastatic transitions.

Show speakers

09:30-10:00 The molecular clutch model as a framework to understand integrin-mediated mechanotransduction

Dr Pere Roca-Cusachs, Institute for Bioengineering of Catalonia, Spain

Abstract

Cell proliferation and differentiation, as well as key processes in development, tumorigenesis, and wound healing, are strongly determined by the physical properties of the extracellular matrix (ECM). In this talk, Pere Roca-Cusachs’ approach combining molecular biology, biophysical measurements, and theoretical modelling to understand matrix rigidity sensing will be addressed. The roles of the properties under force of integrin-ECM bonds, and of the adaptor protein talin, will be discussed. This sensing can be understood through a computational molecular clutch model, which can quantitatively predict the role of integrins, talin, myosin, and ECM receptors, and their effect on cell response. Finally, it will be argued how this molecular clutch framework can explain cell sensing not only of substrate rigidity, but also of ECM spatial distribution of ligands, and how both rigidity and spatial sensing can be understood through the general principle of cell sensing of force loading rates.

Show speakers

10:00-10:30 Crosstalk between fibroblastic stroma and leukocytes controls contractility and matrix remodelling

Dr Sophie Acton, MRC-Laboratory for Molecular Cell Biology, University College London, UK

Abstract

Sophie Acton’s interests lie in the communication between different cell types of the immune system, specifically the mechanisms controlling cellular trafficking, multicellular organisation and lymphoid organ architecture. The Acton lab uses the lymph node as their model system for investigating these processes. The lymph node is a highly organised and tightly controlled environment. The dynamic nature of lymph node swelling and contraction is critical to all immune responses and is not well understood. The group wants to understand the processes involved in lymph node swelling/expansion, and how these changes are coordinated. The interplay between immune cells and non-haematopeotic stromal cells is key to this process. There are many parallels between the cells interacting in the lymph node during an immune response, and the interactions happening in a tumour. Many of the same or similar cell types are present but a tumour is a hugely disorganised mess, and even worse, every tumour is different. One of the major benefits of their research is that they can use the lymph node model to both understand immunity, but also take those findings and apply that knowledge to the same cells in tumours, helping to understand cancer better, and hopefully find ways to harness our immune system to fight and destroy tumours.

Show speakers

10:30-11:00 Coffee break

11:00-11:30 A unified pathway linking microtubules, myosin-II filaments and integrin adhesions

Professor Alexander Bershadsky, Mechanobiology Institute, National University of Singapore, Singapore, and Weizmann Institute of Science, Israel

Abstract

The interrelationship between microtubules and the actin cytoskeleton in mechanoregulation of integrin-mediated adhesions is poorly understood. Here, Alexander Bershadsky shows that the effects of microtubules on two major types of cell-matrix adhesions, focal adhesions and podosomes, are mediated by KANK family proteins connecting the adhesion protein talin with microtubule tips. Both total microtubule disruption and microtubule uncoupling from adhesions by manipulations with KANKs trigger a massive assembly of myosin-IIA filaments. Myosin-IIA filaments, augmenting the focal adhesions and disrupting the podosomes, are indispensable effectors in the microtubule-dependent regulation of integrin-mediated adhesions. Myosin-IIA filament assembly depends on Rho activation by the RhoGEF, GEF-H1, which is trapped by microtubules when they are connected with integrin-mediated adhesions via KANK proteins but released after their disconnection. Thus, microtubule capturing by integrin-mediated adhesions modulates the GEF-H1-dependent effect of microtubules on the myosin-IIA filaments. Subsequent actomyosin reorganisation then remodels the focal adhesions and podosomes, closing the regulatory loop.

Show speakers

11:30-12:00 Assessing the tensional state of fibronectin fibres in cancer stroma

Professor Viola Vogel, ETH Zürich, Switzerland

Abstract

Major transformations of extracellular matrix (ECM) accompany cancer progression, yet it remains poorly understood whether and how the ECM orchestrates the deterioration of healthy to pathological tissues. These processes are regulated by a complex interplay of cells with their ECM, whereby the biochemical composition as well as the physical features of ECM are well recognised to regulate diverse cell functions. Spatial mapping of the strain of ECM fibrils is crucial to learn how fibre stretching correlates with cell signalling events and disease progression. Progress was hampered though due to the lack of nanoprobes capable of sensing cell generated forces or the molecular strains at the tissue level. The Vogel lab thus took advantage of the evolution of bacterial adhesins that specifically target FN with high affinity, but only the relaxed but not stretched fibres, and exploited them to map the strain of ECM fibrils within histological cryosections of tumour stroma and in living animals. Spatial proximity analyses with other biomarkers provide first insights into functional correlations as further discussed in the presentation.

Show speakers

12:00-13:00

Lunch

13:00-17:00

How forces affect cancer genomes

8 talks Show detail Hide detail

13:00-13:15 Introduction to the session

13:15-13:45 Genome variation across cancers scales with tissue stiffness: an invasion-mutation mechanism and implications for immune cell infiltration

Professor Dennis E Discher, University of Pennsylvania, USA

Abstract

Many different types of soft and solid tumours have now been sequenced, and meta-analyses suggest that genomic variation scales with the stiffness of the tumours’ tissues of origin. Since stiff solid tissues have higher density of fibrous collagen matrix, which should decrease tissue porosity, processes in proliferation could be affected and so could invasion into stiff tissues as the nucleus is squeezed sufficiently to enhance DNA damage. Although careful analyses continue to be required for rigorous conclusions about such DNA damage (eg 53BP1 seems a poor marker whereas gH2AX agrees with electrophoresis), diversification of a cancer genome after constricted migration is now clear in vitro and seems to involve loss of DNA repair factors. Understanding genome changes that give rise to neo-antigens is important to selection of cancer cell subpopulations (immunoediting) as well as to the development of immunotherapies. Monocytes/macrophages that might now be engineered to effectively attack cancer cells seem particularly relevant to understanding infiltration into solid tumours as well as the effects of microenvironment stiffness on factors that protect the genome such as the nuclear lamins.

Show speakers

13:45-14:15 Tissue inspired hydrogels to understand breast cancer metastasis and drug resistance

Dr Shelly Peyton, University of Massachusetts Amherst, USA

Abstract

Improved in vitro models are needed to better understand cancer progression and bridge the gap between in vitro proof-of-concept studies, in vivo validation, and clinical application. Many methods exist to create biomaterial platforms, including hydrogels, which Shelly Peyton’s lab use to study cells in contexts more akin to what they experience in vivo. Her lab has multiple approaches to create such biomaterials, based on combinations of poly(ethylene glycol) (PEG) with peptides and zwitterions. In this presentation, Shelly will discuss their findings in using these cell culture environments to understand the role of the extracellular matrix (ECM): ligand density, stiffness, geometry, etc, in controlling cancer cell innate drug response via adaptive signalling.

Show speakers

14:15-14:45 Mechanical regulation of genome organisation and gene expression

Dr GV Shivashankar, Mechnobiology Institute-National University of Singapore, Singapore

Abstract

Cells within the tissue microenvironment are highly heterogeneous and integrate both biochemical and physical signals to maintain homeostasis. However it is unclear how the mechanical constraints on cells (and thus their geometry) affect the micro-environmental regulation of genome programs. To address this question, the Shivashankar lab uses micro-patterned substrates to sculpt cell geometry and study its role in integrating micro-environmental signals such as cytokines and tissue compression. In this talk, GV Shivashankar will discuss an important layer of genome regulation resulting from the coupling between cell geometry and 3D organisation of chromosomes and their intermingling. The lab’s results show that the mechanical state of a cell dictates how cells integrate signals to control gene expression. Importantly, sustained growth of cells on such geometrically confined substrates results in novel routes to nuclear reprogramming and the regulation of cell-fate decisions.

Show speakers

14:45-15:15 Coffee break

15:15-15:45 Squish and squeeze: the role of the nucleus and lamins in breast cancer metastasis

Dr Jan Lammerding, Cornell University, USA

Abstract

During cancer cell invasion and metastasis, tumour cells migrate through interstitial spaces as small as 2 µm in diameter. The deformability of the cell nucleus constitutes a rate-limiting factor in the passage of cells through such confined environments. Intriguingly, the expression of the nuclear envelope proteins lamin A/C, which are a major determinant of nuclear deformability, is misregulated in many cancers. Patient-derived breast tumour tissues and cell lines revealed significantly lower lamin A/C levels than normal tissues, with lamin A/C levels further reduced in particularly aggressive cell lines. Breast cancer cells with low lamin A/C levels had more deformable nuclei and migrated faster through confined environments than cells with high lamin A/C levels. Increasing lamin A expression in metastatic cells with normally low lamin A/C levels decreased cell proliferation and altered expression of proteins involved in cell adhesion, extracellular matrix remodeling, and cell metabolism, indicating additional mechanisms by which lamins can modulate cancer progression and impact both tumour cell invasion and outgrowth. Analysis of breast tumour tissue microarrays revealed that low levels of lamin A/C are associated with reduced disease-free survival. Insights gained from these studies could improve prognostic approaches and motivate novel therapeutic approaches to control metastatic disease in breast cancer.

Show speakers

15:45-16:15 Normalizing transformed cancer cells with cytoskeletal proteins not RTKs

Professor Michael Sheetz, Mechanobiology Institute, National University of Singapore, Singapore

Abstract

A major hallmark of cancer cells is uncontrolled growth on soft matrices (transformed growth), which implies that cancer cells lack the ability to sense matrix rigidity. Our recent studies of fibroblasts show that local contractions by rigidity sensing modules block growth on soft surfaces but module depletion causes transformed growth. The contractile system involves many cytoskeletal proteins that must be correctly assembled for proper rigidity sensing. The Sheetz lab tested the hypothesis that cancer cells lack rigidity sensing due to their inability to assemble contractile modules because of altered cytoskeletal protein levels. In all transformed cancer cells tested, there were over ten-fold fewer rigidity-sensing contractions compared with normal fibroblasts. Restoring normal levels of cytoskeletal proteins restored rigidity sensing and rigidity-dependent growth in transformed cancer cells. In several cases, replenishing tropomyosin 2.1 (often depleted by miR-21) or depleting 3 (often overexpressed) caused normal growth on rigid and anoikis on soft surfaces. The process of anoikis was driven by death-associated protein kinase1 in a Tpm2.1 and talin1 head dependent process that was downstream of PTPN12 (PTP-PEST).  Thus, the depletion of rigidity sensing modules enables growth on soft surfaces by preventing anoikis, which is an important factor in further cancer progression.

Show speakers

16:15-17:00 Closing talk

Dr Chris Bakal, Institute of Cancer Research, UK
Dr Julia Sero, Institute of Cancer Research, UK

Show speakers

Related events