2020 Research Symposium Program

2020 CURE CANCER VIRTUAL RESEARCHER SYMPOSIUM MONDAY 6th JULY 2020  Welcome We are delighted to welcome you to Cure Cancer’s inaugural Virtual Researcher Symposium. As we know, the global pandemic has seen us all adapt the way we work. Although we are disappointed not to be able to bring our researchers together physically this year, we are looking forward to our first ever virtual symposium and hope you will find the day interesting, useful and enjoyable. The Researcher Symposium is an important platform for our early-career researchers to connect with fellow grant recipients and learn about each other’s innovative ideas and approaches to improving the prevention, detection and treatment of all cancers. This year’s event is also an opportunity for our researchers to exercise their skills in presenting scientific research in layman’s terms – something that is becoming increasingly important in today’s competitive grant application environment. Cure Cancer identifies research projects with the best possible chance of finding a cure, and funds you; the emerging research stars of tomorrow, all whom are fearless in their development and exploration of ground-breaking ideas. We are incredibly proud to be associated with such an inspiring group of emerging researchers. As part of our grant award program, Cure Cancer also focusses on providing professional development and mentorship to our grant recipients. This year we are privileged to have excellent guest speakers James Butler, Chair of Cancer Council NSW’s Consumer Research review panel, Lisa Greissl, Cure Cancer Fundraiser and Big Hug Box Founder and Professor Carolyn Mountford, Professor of Radiology, Queensland University of Technology. We’d also like to thank Hugh Kearns from Thinkwell for providing his expertise on staying well and being productive. A special thank you to the Symposium Research Organising Committee; Dr Paul Beavis (Peter MacCallum Institute), A/Prof Michael Doran (Queensland University of Technology), A/Prof Viive Howell (Kolling Institute, The University of Sydney) and Dr Susan Woods (South Australian Health and Medical Research Institute (SAHMRI)) for their support of this event and to all of those attending today. Kind Regards, Nikki Kinloch Chief Executive Officer Cure Cancer 2  Program MONDAY 6th JULY 9.00am Welcome - A/Prof Ilona Cunningham, Chair, Cure Cancer Research Committee 9.05am Welcome - Nikki Kinloch, CEO, Cure Cancer 9.25am SESSION 1 9.25am Session Chair: Dr Paul Beavis, Peter MacCallum Institute 9.30am Dr Arutha Kulasinghe, Queensland University of Technology Spatial profiling of the tumour microenvironment 9.35am Dr Simone Park, The University of Melbourne Targeting tissue-resident memory T cells in cancer immunotherapy 9.40am Dr Fernando Guimaraes, University of Queensland Diamantina Institute Therapeutic blockade of TGF-b superfamily members improves natural killer cell function and anti-cancer immunity 9.45am 9.50am 9.55am Dr Jessica Da Gama Duarte, Olivia Newton-John Cancer Research Institute Predicting immunotherapy outcomes in rare cancers Dr Melissa Cantley, The University of Adelaide and SAHMRI Biomarker discovery using novel proteomics to enable identification of high-risk smouldering myeloma patients Q&A Session with Dr Paul Beavis and Session 1 Researchers 10.10am James Butler: Consumer Advocate 10.20am Q&A Session with James Butler and Nikki Kinloch 10.30am BREAK 10.45am SESSION 2 10.45am Session Chair: A/Prof Viive Howell, Kolling Institute, The University of Sydney 10.50am Dr Kate Vandyke, University of Adelaide N-cadherin inhibitors as vascular disrupting agents: increasing drug delivery to tumours and improving quality of life for cancer patients 10.55am Dr Nathalie Bock, Queensland University of Technology Bioengineered humanised models: A novel preclinical platform for bone metastatic cancer research 11.00am Dr Rachel Thijssen, The Walter and Eliza Hall Institute of Medical Research Single cell analyses reveal unexpected and complex heterogeneity in leukaemia relapse on venetoclax 11.05am Dr Laurence Cheung, Telethon Kids Institute and Curtin University Dissecting the Bone Marrow Microenvironment in pre-B Acute Lymphoblastic Leukaemia 11.10am Dr Shuai Li, The University of Melbourne Integrating epigenomics and genomics to understand the causal pathways and mechanisms of how menarche and menopause modify breast cancer risk 11.15am Q&A Session with A/Prof Viive Howell and Session 2 Researchers 3  Program 11.40am Lisa Greissl: Cure Cancer Ambassador, Cancer Survivor and Founder of Big Hug Box 11.50am Q&A Session with Lisa Greissl and Nikki Kinloch 12.00pm Prof Carolyn Mountford, Queensland University of Technology 12.20pm BREAK 12.50pm SESSION 3 12.50pm Session Chair: Dr Susan Woods, South Australian Health and Medical Research Institute (SAHMRI) 12.55pm 1.00pm 1.05pm Dr Marlene Hao, University of Melbourne A gut feeling about new therapies for glioma treatment: lessons from the enteric nervous system Dr Niantao Deng, Garvan Institute of Medical Research Understanding breast cancer patients’ response to neoadjuvant chemotherapy at single-cell resolution Dr Jessica Holien, RMIT University Network informed analysis of Mucinous Ovarian Carcinoma (#179) 1.10pm Dr Kelly Brooks, QIMR Berghofer Investigating PARP inhibitors for the treatment of SF3B1 mutant melanomas 1.15pm Dr Mark Adams, Queensland University of Technology Exploiting cell cycle factors to enhance chemotherapy response for non-small cell lung cancer patients 1.20pm Dr Laura Edgington-Mitchell, University of Melbourne Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2 1.25pm Q&A Session with Dr Susan Woods and Session 3 Researchers 1.40pm Hugh Kearns, Thinkwell: Staying well and being productive 3.40pm Best Presentation Award 3.45pm Summary of day - A/Prof Mike Doran, Queensland University of Technology 3.55pm Close - Nikki Kinloch, CEO, Cure Cancer 4  Organising Committee Dr Paul Beavis Group Leader, Junior Faculty, Peter MacCallum Institute, Melbourne Dr Paul Beavis completed his PhD at Imperial College London in 2010 and joined the Peter MacCallum Cancer Centre in Melbourne shortly thereafter, partially funded by Cure Cancer, to work in the Cancer Immunology Program. Since his recruitment to Peter Mac, Paul has established a vibrant program of research focussing on the molecular and biological processes involved in tumour-induced immunosuppression, in particular the role of CD73 and adenosine receptor signalling. He also has a significant interest in developing novel CAR T cell technology to enhance their effectiveness in solid cancer. He is a fundamental cancer researcher and immunologist, but his work clearly has a strong translational focus and his collaborative research studies with industry partners and with internal collaborators have provided the foundation for clinical application of his work. Associate Professor Michael Doran NHMRC CDF2 Research Fellow, School of Biomedical Sciences Queensland University of Technology, Brisbane Dr Mike Doran is an NHMRC Fellow and Associate Professor at QUT. Doran completed a BSc (Genetics) and BEng (Chemical) at the University of Alberta (Canada), and PhD (Biomedical Engineering) at the University of New South Wales. Doran’s laboratory is located at the Translational Research Institute. His research interests include study of bone, bone marrow, cartilage, cancers that metastasise to the bone, and research into research. Doran is the Stem Cells and Tissue Engineering Program Leader at QUT, Consultant Scientist at the National Institutes of Health (NIH, Bethesda, USA), TRI/QUT Wellness Ambassador, and on the Cure Cancer Research Committee. 5  Organising Committee (continued) Associate Professor Viive Howell Research Director, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney A/Prof Howell is a molecular geneticist with expertise in in vivo modelling. Her research encompasses a number of cancers including brain, ovarian, thoracic and gastro-intestinal cancers. She is currently establishing preclinical pipelines for these cancers to test new therapeutics alone or in combination with radiotherapy or chemotherapy. Working closely with clinical and surgical colleagues the goal of this research is to fast-track efficacious regimens to clinical trials, identify prognostic and predictive biomarkers and determine strategies to overcome chemoresistance. Dr Susan Woods Senior Research Fellow, South Australian Health and Medical Research Institute (SAHMRI), Adelaide Susan is a mid-career investigator with three co-first author Nature journal publications in the field of cancer research. The focus of her Gut Cancer group at the University of Adelaide is on improving detection methods and treatment for gastrointestinal tract cancers. She trained with Nobel Laureate J. Michael Bishop at University of California San Francisco and with Prof Nick Hayward at QIMR-Berghofer in Brisbane, specialising in genetic alterations found in cancer. She is now working closely with clinician-scientist A/Prof Dan Worthley at SAHMRI, in Adelaide. She uses both patient samples and sophisticated preclinical models. Her research integrates next-generation sequencing data, modelling genomic alterations using CRISPR/Cas9 gene editing and organoid culture to address clinical needs for bowel cancer. This has led to the development of a personalised medicine screening platform to guide patient-specific treatment for patients with advanced colorectal cancer. 6  Speakers Associate Professor Ilona Cunningham MBBS FRACP Haematologist Ilona Cunningham is past head of Haematology at Concord Hospital, a partnership of eight Haematologists. She is one of a number of cancer specialists, who has worked tirelessly to establish the Concord Cancer Centre and is a vocal advocate for holistic, multidisciplinary care for cancer patients in the local community. She successfully lobbied for a state of the art building for the Concord Cancer Centre, which will be completed in 2021. It will ensure cutting edge clinical care for cancer patients, including radiotherapy and clinical trials. She is a member of the Medical Staff Council Executive and past Chair of the Medical Staff Council at Concord and continues to advocate for Stage 2 of the redevelopment of Concord Hospital, to benefit all patients. In her role as practising haematologist and Board Member of the ANZAC Research Institute, she is strongly committed to supporting basic, translational and clinical, ie bench to bedside research, to enable doctors to deliver worldclass care to patients. Ilona trained in Melbourne and at Stanford University in California as a post-doctoral fellow in Haematology. She is a fellow of the Royal Australian College of Physicians and a member of a number of organisations, including the Australasian Leukaemia and Lymphoma Group and the American Society of Haematology. Ilona has a long-standing and active interest in clinical research in Myelodysplasia and AML in elderly patients, Myeloproliferative Neoplasms, CML and other haematologic malignancies as well as ITP. James Butler Chair, Cancer Council NSW's Consumer Research review panel James is currently Chair of Cancer Council NSW’s Consumer Research review panel and a former chair of the Hills Community Cancer Network. Mr Butler is a retired businessman having been in business for over 30 years. He is an active consumer representative on cancer services committees in Western Sydney Local Health District. James has been an active volunteer for Cancer Council NSW for over 20 years, holding roles including Chair of The Hills Relay For Life Organising Committee and Chair of Western Sydney Cancer Advocacy Network. As a two time cancer survivor, he understands the need to influence decision makers around key issues that have an impact on people affected by cancer. 7  Speakers (continued) Lisa Greissl Cure Cancer Fundraiser & Ambassador, The Big Hug Box Founder Lisa Greissl is a wife and mum of two girls who, shortly after the birth of her second daughter, was diagnosed with a rare and malignant cancer on her spine in 2015. When her life should have been focused on motherhood, it was instead focused on fighting for her life. Although based in Newcastle, Lisa was extremely fortunate to be referred to a team of specialists down in Sydney which included Cure Cancer Alumni Professor Tattersall. Professor Tattersall, which Lisa also called “The Prof” shared just before commencing treatment that although he hadn’t seen this type of tumor before he remained confident and his approach would be a little “left of field". Despite the odds, and to the surprise of many, Lisa received the unexpected news that she was cancer free in February 2016 and so now dedicates her life passionately to supporting cancer research in hope to save more lives just like hers. In understanding the importance of research, all Lisa’s family began to give generously. In looking for a broader way to raise funds and awareness of research Lisa came up with the idea to create The Big Hug Box. The Big Hug Box, founded in 2018 supports cancer patients through a practical and empowering gift box. From all sales it was decided that 100% of proceeds would go to Cure Cancer. The Big Hug Box has now become more than just a gift but a community who share a common passion for empowering patients through our Big Hug Boxes. Whilst Lisa’s goal was to initially sell 20 boxes, The Big Hug Box continues to grow and have already sold close to 700 boxes that have been sent to patients Australia wide. With all proceeds donated directly back to Cure Cancer, Lisa says that her charity enables the community to give not only their loved ones a big hug, but also our amazingly dedicated cancer researchers. 8  Speakers (continued) Professor Carolyn Mountford MSc(Oxon) DPhil(Oxon) MS(Harv) Professor of Radiology, Queensland University of Technology Professor Carolyn Mountford is an Oxford Educated Biophysicist. She recently stepped down as CEO and Director of Research for Australia’s Translational Research Institute. Carolyn was awarded full Professor of Radiology at Harvard Medical School in 2011 and retains a position as NeuroScientist at the Athinoula A. Martinos Center for Biomedical Imaging at MGH and Harvard Medical School. She is currently Professor of Radiology at QUT and CEO of a start up DatChem. Professor Mountford and her team have been a worldwide development site for Siemens since 1999. She is a co-inventor of the diagnostic protocol to monitor women at high risk for breast cancer identifying metabolic deregulations in their breast tissue that precede tumour growth. The same technology is shown to identify changes to the brain associated with learning, memory, Post-Traumatic Stress Disorder (PTSD) and injury from blast and impact. Her team is under contract to the USA and Australian military to develop this approach to improve the health of soldiers. Hugh Kearns Thinkwell Hugh Kearns is recognised internationally as a public speaker, educator and researcher. He regularly lectures at universities across the world and has recently returned from lecture tours of the UK and the US which included lectures at Oxford, Cambridge, Harvard, Berkeley and Stanford. His areas of expertise include self-management, positive psychology, worklife balance, learning and creativity. He draws on over twenty five years of experience as a leading training and development professional within the corporate, financial, education and health sectors in Ireland, Scotland, North America, New Zealand and Australia. He has coached individuals, teams and executives in a wide range of organisations in the public and private sectors. Hugh lectures and researches at Flinders University, Adelaide, Australia. He is widely recognised for his ability to take the latest research in psychology and education and apply it to high-performing people and groups. As a coauthor with Maria Gardiner, he has published ten books which are in high demand both in Australia and internationally. 9  List of abstracts (in order of presentation) Dr Arutha Kulasinghe NHMRC Early Career Research Fellow Institute: Queensland University of Technology at the Translational Research Institute Email address: Arutha.kulasinghe@qut.edu.au Grant funded by our principal supporter, the Can Too Foundation. Spatial profiling of the tumour microenvironment 1. School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland, University of Technology, Brisbane, QLD, Australia. 2. Translational Research Institute, Woolloongabba, QLD, Australia. Arutha Kulasinghe1,2 Immune checkpoint inhibitors (ICI) have Rather, a number of immune cell types/ shown durable and long-term benefits in activation status were found to correlate a subset of head and neck squamous cell with progressive disease. This study, to carcinoma (HNSCC) patients. our knowledge, represents the first spatial analysis of HNSCC tumours. To identify patient-responders from nonresponders, biomarkers are needed which Current Research Interests: are predictive of outcome to ICI therapy. Spatial profiling of the tumour Cues in the tumour microenvironment microenvironment, liquid biopsy, head (TME) have been informative in and neck cancers, lung cancers, understanding the tumour-immune predictive biomarkers of response to contexture. In this study, the NanoString immunotherapy. GemoMx™ Digital Spatial Profiling (DSP) technology was used to determine the Keywords: immune marker and compartment specific Head and neck cancer, lung cancer, measurements in a cohort of HNSCC tumour microenvironment, digital spatial tumours from patients receiving ICI profiling, circulating tumour cells. therapy. Our preliminary findings revealed that markers involved with immune cell infiltration (CD8 T-cells) were not predictive of outcome to ICI therapy. 10  List of abstracts (continued) Dr Simone Park Research Fellow Institute: The University of Melbourne at the Peter Doherty Institute for Infection and Immunity Email address: simone.park@unimelb.edu.au Grant co-funded with Cure Cancer, Cancer Australia and 50% funded by our principal supporter, the Can Too Foundation. 1. Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia, 3000 Targeting tissue-resident memory T cells in cancer immunotherapy Simone L. Park1, Stephane Guillaume1, Maleika Osman1, Laura K. Mackay1 The immune system is critical to inhibit the development and spread of cancer with T cells being central to this process. Immunotherapies that target T cells have greatly advanced the treatment of solid cancers including melanoma, but current strategies are not universally effective. Design of novel treatment strategies will require a better understanding of how effective anti-tumour T cell responses are generated and controlled. Tissue-resident memory T (TRM) cells are a population of non-recirculating immune cells that reside permanently in non-lymphoid peripheral tissues and can potently inhibit cancer growth. These cells have been identified in a variety of solid human cancers where they correlate with improved patient survival. The goal of this project is to determine whether the efficacy of cell-based immunotherapies can be improved by boosting TRM cell formation in tumours. We will combine a novel orthoptic melanoma model that we have established in mice with gene editing technologies 11 to devise novel strategies to enhance the generation of tumour TRM cells. We will assess the ability of chimeric antigen receptor (CAR) TRM cells to form in the tumour microenvironment and ask whether increasing the generation and activity of CAR TRM cells can enhance protection against solid cancers. By addressing these aims, we hope to identify novel pathways that direct formation of protective TRM cells in tumours and uncover ways to artificially enhance their generation using immunotherapy. These insights will therefore unlock new avenues to develop more effective cancer treatments. Current Research Interests: Immunotherapy, T cells, immune memory, tissue-resident memory, solid cancers. Keywords: Immunotherapy, CAR T cells, melanoma, solid cancers, T cells.  List of abstracts (continued) Dr Fernando S. F. Guimaraes Group Leader Institute: University of Queensland Diamantina Institute Email address: f.guimaraes@uq.edu.au Grant co-funded with Cure Cancer, Cancer Australia and 83% funded by the Can Too Foundation. 1. University of Queensland Diamantina Institute. Brisbane/ Australia Therapeutic blockade of TGF-b superfamily members improves natural killer cell function and anti-cancer immunity. Fernando Souza-Fonseca-Guimaraes1 Natural killer (NK) cells are innate Activin-A, phosphorylates SMAD2/3 to lymphocytes that play a major role in efficiently suppress IL-15-mediated NK immunosurveillance against tumour cell metabolism. Activin-A impairs human initiation and metastatic spread. and mouse NK cell proliferation and downregulates intracellular granzyme B The signals and checkpoints that regulate levels to impair tumour killing. Similar to NK cell fitness and function in the tumour TGF-b, Activin-A also induces SMAD2/3 microenvironment are not well defined. phosphorylation and drives NK cells to Transforming growth factor (TGF)-b is a upregulate several innate lymphoid cell recognized suppressor of NK cells that (ILC)1-like surface markers. Further, inhibits IL-15-dependent signalling and Activin-A also induces these changes induces cellular transdifferentiation. on TGF-b receptor deficient NK cells, highlighting that Activin-A and TGF-b are Computational analyses of an NK cell gene independent pathways that can drive signature in metastatic melanoma showed SMAD2/3-mediated NK cell suppression. that higher NK cell infiltration is associated Finally, therapeutic inhibition of Activin-A with improved patient survival and this by Follistatin significantly slows orthotopic effect is ablated in patients where there is melanoma growth in mice. These data evidence of active TGF-b signalling. This highlight the relevance of examining suggests that a subset of patients would TGF-b-independent SMAD2/3 signalling benefit from therapies that can prevent mechanisms as a novel therapeutic axis to pSMAD2/3, however, in NK cells the role of relieve NK cell suppression and promote other SMAD signalling pathways that act tumor immunity. downstream from the TGF-b superfamily is unknown. Here, we show that NK cells Current Research Interests: also express the type I Activin receptor, Immunotherapy, cancer metastases, cancer ALK4, which upon binding its ligand immunosuppression, natural killer cells. 12  List of abstracts (continued) Dr Jessica Da Gama Duarte Postdoctoral Research Fellow Institute: Olivia Newton-John Cancer Research Institute Email address: Jessica.Duarte@onjcri.org.au Grant funded by Cure Cancer through the Cancer Australia Priority-driven Cancer Support Scheme. Year one of her grant is in Memory of Micaela Virgona. Predicting immunotherapy outcomes in rare cancers Jessica Da Gama Duarte1,2, Jonathan Cebon1,2, Oliver Klein1,2, Andreas Behren1,2 1. Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 2. School of Cancer Medicine, La Trobe University, Heidelberg, Victoria Effective immune engagement with a tumour occurs when immune cells recognize, and destroy malignant cells. However, tumours have developed multiple ways of escaping immune attack, often leading to uncontrolled tumour growth1. In general, patients with evidence of strong immune engagement have a large number of anti-tumour immune cells within their tumours, and improved clinical responses to treatments targeting the immune system (immunotherapy), when compared to those without2. Serological cancer-specific antibodies produced by B cells upon malignant cell recognition are a form of immune engagement that have been proposed to stratify patients and predict treatment response3. However, when produced in excess, antibodies may contribute to autoimmune-like conditions typical of immunotherapy toxicities4,5. A custom protein microarray able to detect antibodies This study aims to identify predictive against over 100 tumour markers in biomarkers of response and toxicity parallel using only one drop of blood using the microarray technology, and with high sensitivity was developed6. to compare findings to a large suite of biomarker studies being performed in Rare cancers have limited therapeutic parallel. options, low survival and are often excluded from clinical trials and Current Research Interests: biomarker studies due to their low Immunotherapy, B cell immunology, incidence. However, while incidence tumour immunology, protein is low for each individual rare cancer, microarrays, personalised medicine, collectively they comprise of almost predictive/diagnostic/prognostic a third of all cancer diagnoses, cancer biomarkers. highlighting the need for novel therapies. A recent clinical trial Keywords: investigates the use of combined Immunotherapy, rare cancers, protein immune checkpoint blockade (ICB) microarrays, autoantibodies. in 60 cancer patients with rare upper gastrointestinal malignancies, neuroendocrine tumours and gynaecological tumours, with previously unprecedented clinical responses (31%) and disease control (31%), independent of tumour type. However, this combination yielded treatment-induced toxicities, which led to treatment cessation in a proportion of patients (22%). As such, the ability to predict the likelihood of clinical response and toxicity onset is of the utmost value for adequate patient stratification and clinical 1. Da Gama Duarte J, Woods K, Andrews MC, Behren A. The good, the (not so) bad and the ugly of immune homeostasis in melanoma. Immunol Cell Biol. 2018 Feb 2;1–10. 2. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321–30 3. Yuan J, Hegde PS, Clynes R, Foukas PG, Harari A, Kleen TO, et al. Novel technologies and emerging biomarkers for personalized cancer immunotherapy. J Immunother cancer. Journal for ImmunoTherapy of Cancer; 2016;4(1):3. 4. Da Gama Duarte J, Parakh S, Andrews MC, Woods K, Pasam A, Tutuka C, et al. Autoantibodies May Predict ImmuneRelated Toxicity: Results from a Phase I Study of Intralesional Bacillus Calmette-Guérin followed by Ipilimumab in Patients with Advanced Metastatic Melanoma. Front Immunol. 2018;9(March):411. 5. Gowen MF, Giles KM, Simpson D, Tchack J, Zhou H, Moran U, et al. Baseline antibody profiles predict toxicity in melanoma patients treated with immune checkpoint inhibitors. J Transl Med. BioMed Central; 2018;16(1):82 6. Beeton-Kempen N, Duarte J, Shoko A, Serufuri J-M, John T, Cebon J, et al. Development of a novel, quantitative protein microarray platform for the multiplexed serological analysis of autoantibodies to cancer-testis antigens. Int J cancer. management. 2014 Oct 15;135(8):1842–51. 13  List of abstracts (continued) Dr Melissa Cantley NHMRC Early Career Research Fellow Institute: The University of Adelaide and SAHMRI Email address: melissa.cantley@adelaide.edu.au Grant co-funded by Cure Cancer with Cancer Australia and Leukaemia Foundation. Biomarker discovery using novel proteomics to enable identification of high-risk smouldering myeloma patients 1. Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 2. Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide 3. Mass Spectrometry Core Facility, South Australian Health and Medical Research Institute, Adelaide 4. Cancer Sciences Unit, Faculty of Medicine, University of Southampton, UK 5. Australian Centre for Blood Diseases, Monash University, Victoria 6. Proteome Exploration Laboratory, Beckman Institute, Californian Institute of Technology (Caltech), USA 7. Central Adelaide Local Health Network, Adelaide, Australia Melissa Cantley1,2, Kate Vandyke1,2, Marten Snel3, Surinder Sahota4, Andrew Spencer5, Spiros Garbis6 and Andrew Zannettino1,2,7 common haematological cancer. MM to enable early therapeutic intervention. is preceded by largely asymptomatic stages known as monoclonal The goal of this study is to utilise our gammopathy of undetermined existing extensive biobank of peripheral significance (MGUS) and smouldering blood plasma collected from over 1500 myeloma (SMM). patients with MGUS, SMM and active MM, in combination with state-of- Currently, the standard of care is to the-art quantitative high-precision treat patients when they progress proteomics technologies. This novel to symptomatic, active MM, a point approach will enable the identification at which there is evidence of end- of protein biomarkers that are organ damage that is, in many cases, associated with disease progression. irreversible. Utilizing this current model This will result in the development of of treatment, the disease is incurable, a minimally invasive, peripheral blood- with only 50% of patients surviving 5 based test to predict SMM patients years from diagnosis. at high-risk of progression enabling earlier treatment to improve treatment Despite the growing number of responses, patient quality of life and trials highlighting the benefit of overall survival. early treatment in SMM patients, the use of anti-myeloma therapies Current Research Interests: Multiple Myeloma (MM) is a in this cohort of patients is not Multiple myeloma, bone loss, haematological malignancy currently recommended due to their smouldering myeloma, bone characterized by the uncontrolled unfavourable toxicity profiles. There is microenvironment. proliferation of clonal plasma cells substantial heterogeneity that exists in (PCs) in the bone marrow (BM). the SMM cohort, with 30% considered Keywords: at high-risk of progression within 2 Smouldering myeloma, Multiple Approximately 140,000 people years of diagnosis. However, no robust myeloma, Disease progression, worldwide are diagnosed with MM biomarkers have been defined that can Biomarkers, Proteomics each year, making it the second most identify those high-risk SMM patients 14  List of abstracts (continued) Dr Kate Vandyke Cancer Council Beat Cancer Early Career Research Fellow Institute: University of Adelaide Email address: kate.vandyke@adelaide.edu.au Grant co-funded by Cure Cancer with Cancer Australia and Leukaemia Foundation. N-cadherin inhibitors as vascular disrupting agents: increasing drug delivery to tumours and improving quality of life for cancer patients 1. Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia 2. Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia 3. Division of Urology, McGill University, Montreal, Canada 4. Centre for Nanoscale BioPhotonics, University of Adelaide, Adelaide, Australia 5. Vascular Biology and Cell Trafficking Laboratory, Centre for Cancer Biology, University of South Australia, Adelaide, Australia Kate Vandyke1,2, Krzysztof M. Mrozik1,2, Duncan R. Hewett1,2, Jacqueline E. Noll1,2, Khatora S. Opperman1,2, Orest W. Blaschuk3, Mark Hutchinson4, Claudine Bonder5, Andrew C.W. Zannettino1,2 Introduction: N-cadherin is a homotypic cell-cell adhesion and signalling molecule which plays an important role in maintaining endothelial barrier integrity and controlling vascular permeability. Previous studies have demonstrated that the N-cadherin blocking peptide ADH-1 increases vascular permeability and chemotherapeutic drug delivery to the tumour microenvironment. Here, we have evaluated the effects of a small molecule ADH-1 peptidomimetic, LCRF-0006, on blood vessel integrity and permeability. Additionally, we have assessed the ability of LCRF-0006 to increase the efficacy of the anti-cancer agent bortezomib in a mouse model of the haematological cancer multiple myeloma (MM). < 0.001; co-efficient of drug interaction < 0.7). Methods: In vitro vascular disruption and permeability assays were performed using the human bone marrow endothelial cell line TrHBMEC. Druginduced cell apoptosis was assessed by flow cytometry using Annexin V and 7-AAD. The therapeutic utility of LCRF-0006 (100mg/kg) alone, and in combination with a sub-therapeutic dose of bortezomib (0.5mg/kg), was evaluated in the syngeneic C57Bl/ KaLwRij/5TGM1 mouse model of MM. Conclusion: These findings demonstrate the potential utility of LCRF-0006 to increase bortezomib efficacy in vivo. Future studies will investigate whether LCRF-0006 can be used to increased tumour-specific update of bortezomib and other anti-myeloma therapies, thereby decreasing the off-target sideeffects of these treatments. Results: LCRF-0006 disrupted preformed endothelial tubes and rapidly disrupted cell-cell junctions in confluent endothelial monolayers in a reversible manner in vitro. Additionally, LCRF0006 increased monolayer permeability to FITC-dextran in vitro, suggesting enhanced vascular permeability following LCRF-0006 treatment. LCRF-0006 treatment once daily for 4 weeks was well-tolerated in C57Bl/ KaLwRij mice, with no effect on body weight, haematopoiesis, or bone marrow osteoblast, mesenchymal stromal cell or endothelial cell numbers. Notably, LCRF-0006 synergistically increased MM tumour response to a low dose of the anti-MM agent bortezomib, leading to regression of disease in 5 of 5 mice (P 15 Current Research Interests: Dr Vandyke's current research interests involve elucidating the molecular and cellular mechanisms responsible for disease progression in the haematological cancer multiple myeloma. In particular, her research focusses on why up to one quarter of patients have rapidly progression or rapid relapse following therapy, leading to death within three years of initial diagnosis. These studies primarily focus on investigating the mechanisms controlling myeloma dissemination and the identification of novel therapeutic targets to improve response to antimyeloma therapies. Keywords: multiple myeloma, N-cadherin, vascular permeability, bortezomib  List of abstracts (continued) Dr Nathalie Bock Research Fellow Institute: Institute of Health and Biomedical Innovation (IHBI), Translational Research Institute (TRI), Queensland University of Technology (QUT) Email address: n.bock@qut.edu.au Grant co-funded with Cure Cancer, Cancer Australia and 66% by our principal supporter, the Can Too Foundation. 1. Queensland University of Technology, Brisbane, Queensland, Australia Bioengineered humanised models: A novel preclinical platform for bone metastatic cancer research Nathalie Bock1, Jacqui McGovern1, Jenni Gunter1, David Waugh1, Dietmar Hutmacher1 Prostate cancer (PCa) is the most adiposity. Considering that the bone the presence of human bone marrow commonly diagnosed cancer in microenvironment itself is highly fatty fat, and used to assess whether co- Australia (estimated 16,665 new in old people, bone marrow adipocytes targeting drugs may be an effective cases in 2017). Whilst survival rates may be pivotal in PCa progression. therapeutic strategy against CRPC. therapies, cancer adaptation and Importantly, despite successful Current Research Interests: acquired resistance continues to be a testing in mouse studies, more than Cancer Models, Bioengineering Models, major therapeutic problem. 80% of novel drug candidates fail Biomimetic Cell Culture Models; have improved as a result of targeted to prove their efficacy when tested Patient-Derived Explants; Patient- The current treatment upon in humans [7]. Traditional mouse Derived Xenografts (PDX), Organoid unsuccessful chemical androgen models are unable to fully recapitulate Models, In Vitro Tumor Models, In Vivo deprivation therapy (ADT) is the use the physiological or pathological Tumor Models, Humanised Mouse of androgen-targeted therapies (ATT). processes in humans and one of Models, Preclinical Models, Bone, While PCa initially responds, the the key challenges in the field of Bone Metastasis, Prostate Cancer, development of castrate-resistant PCa translational medicine is to “make the Breast Cancer, 3D Imaging, Tissue (CRPC) is inevitable and PCa thrives in mouse organism more human” [8]. Engineering, Biomaterials, Drug Testing, Targeted Therapy; Personalised the bones, the primary metastatic site and incurable condition. This project will be focusing on this Medicine, Tumor Microenvironment. key area by implementing a humanised In the bone microenvironment, in vitro 3D model (including human Keywords: adipocytes contribute actively to osteoblasts and adipocytes cultured Cancer Models, Microtissue bone function. In the context of ADT, a in 3D) in a mouse model, in order Bioengineering, Bone Metastasis, main side-effect is the development to recreate a humanised fatty bone Humanised Mouse Models. of metabolic dysfunction, including metastatic niche in vivo. The model insulin resistance and increased will be confirmed using ADT/ATT in 16  List of abstracts (continued) Dr Rachel Thijssen Postdoctoral fellow Institute: The Walter and Eliza Hall Institute of Medical Research Email address: thijssen.r@wehi.edu.au Grant co-funded with Cure Cancer, Cancer Australia and 50% funded by our principal supporter, the Can Too Foundation. Single cell analyses reveal unexpected and complex heterogeneity in leukaemia relapse on venetoclax R. Thijssen1,2, L. Tian1,2, C. Flensburg1,2, C.E. Teh1,2, M.A. Anderson1,2,3,4, H.K. Peng1,2, 1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC. 3052 Australia 2. University of Melbourne, Melbourne, VIC. 3004 Australia 3. Royal Melbourne Hospital, Parkville. VIC. 3050. Australia 4. Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia P. Blombery3,4, D.H.D. Gray1,2, I.J. Majewski1,2, M.E. Ritchie1,2, D.C.S. Huang1,2, A.W. Roberts1,2,3,4 Venetoclax, the pro-survival BCL2 inhibitor, is highly effective for the treatment of chronic lymphocytic leukaemia (CLL), a disease marked by BCL2 overexpression. However, the disease will eventually progress in most patients after years on venetoclax monotherapy and further treatment options are often limited. Thus, there is an urgent need to fully define the molecular mechanisms driving venetoclax resistance. Using paired samples from patients who have progressed while on venetoclax, all the relapse samples were less sensitive to the drug in vitro indicating that cell intrinsic changes must drive acquired resistance. One such change is the acquired BCL2 G101V mutation which blocks venetoclax binding (Blombery et al. Taken together, our findings reveal Cancer Discov 2019). However, cells that multiple mechanisms must bearing this mutation only account operate to allow acquisition of for a fraction of the tumour cells venetoclax resistance. A detailed at disease progression, strongly understanding of how venetoclax fails implicating other mechanisms must is important for developing strategies operate to subvert the action of to avoid emergence of resistance venetoclax. and to optimally use these powerful anti-cancer agents as part of up-front We applied the state-of-the art therapeutic options for this disease. technology - Cellular indexing of transcriptomes and epitopes in single Current Research Interests: cells (CITE-seq) - which allows us to My goal is to apply single cell fully characterize the tumour cells on techniques (e.g. single cell RNA- the basis of proteomics data and gene seq, CyTOF) to identify all of the expression data, from short-read and mechanisms of resistance that full length-read scRNA-seq. We have have significant implications for identified other drivers of venetoclax how venetoclax is best used, both resistance: intriguingly, high BCLxL in preventing the development of gene expression marked a distinct therapy resistance, and by developing sub-population of tumour cells from strategies to tackle resistance. a cluster harbouring the BCL2 G101V Ultimately, this project should mutation in one patient. These have significantly improve outcomes for unique transcriptional signatures. patients with CLL. Using mass spectrometry (CyTOF), we have now detected high BCLxL in 5 Keywords: out of 15 patients. In these, there was B-cell leukaemia, apoptosis, no evidence for BCLxL amplification or venetoclax, single cell RNA-seq, mutation. CyTOF. 17  List of abstracts (continued) Dr Laurence Cheung Senior Research Officer and Senior Lecturer Institute: Telethon Kids Institute and Curtin University Email address: Laurence.cheung@telethonkids.org.au Grant co-funded by Cure Cancer with Cancer Australia and Leukaemia Foundation. Dissecting the Bone Marrow Microenvironment in pre-B Acute Lymphoblastic Leukaemia Laurence Cheung1,2, Anastasia Hughes1,2, Patrycja Skut1, Rishi Kotecha1-3 1. School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Australia 2. Telethon Kids Institute, The University of Western Australia, Perth, Australia should be treated at diagnosis, and leukaemia burden and prolonged whether such treatments would have survival compared to control mice. any impact on leukaemia progression. In addition, we showed that the 3. Perth Children’s Hospital, Perth, Australia We hypothesise that restoring the combination of tyrosine kinase inhibitor healthy BMM can hinder leukaemia therapy and ZA significantly improved progression and further, that targeting survival compared to TKI therapy alone. Acute lymphoblastic leukaemia (ALL), both leukaemia cells and bone cells In conclusion, our study reveals the the most common childhood cancer, simultaneously is an effective strategy impact of pre-B ALL development on represents over one quarter to treat BCR-ABL1+ ALL. haematopoiesis, bones and the BMM. of paediatric cancer diagnoses. We have developed an Our findings provide evidence for immunocompetent mouse model targeting leukaemia-induced bone Unfortunately, children harbouring of BCR-ABL1+ pre-B ALL that has loss as a novel therapeutic strategy for high-risk genetic alterations in their enabled comprehensive investigation patients. ALL cells such as the BCR-ABL1+ of the architecture of the BMM during fusion gene have dismal prognoses. leukaemogenesis. We found that Current Research Interests: haematopoiesis was perturbed, B • Develop leukaemia preclinical models The microenvironments of leukaemia lymphopoiesis was impaired, collagen • Single cell RNA sequencing to and cancer are critical for multiple production was reduced, and the dissect the leukaemia bone marrow stages of malignancies and they number of osteoblastic cells was microenvironment are an attractive therapeutic target. decreased in the BMM. • Using flow cytometry to enumerate subpopulations of cells in the Clinical studies in children diagnosed with ALL have clearly demonstrated Moreover, leukaemia-bearing mice defects in the bone marrow exhibited severe bone loss during microenvironment (BMM), yet little leukaemogenesis, which is consistent Keywords: is known about the contribution of with clinical data in paediatric ALL. • Leukaemia the normal bone marrow cells during We demonstrated that zoledronic • Bone marrow microenvironment the development of this disease, it’s acid acid (ZA) is effective at reducing • Hematopoiesis progression and relapse. Further, it trabecular bone loss during leukaemia • Preclinical cancer models remains unclear whether the clinical development. Further, mice treated • Flow cytometry symptoms of increased bone fragility with ZA showed significantly lower 18 microenvironment  List of abstracts (continued) Dr Shuai Li Victorian Cancer Agency Early Career Research Fellow Institute: Centre for Epidemiology and Biostatistics, The University of Melbourne Email address: shuai.li@unimelb.edu.au Grant funded by our principal supporter, the Can Too Foundation. 1. 1Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia 2. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia 3. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia 4. Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia. Integrating epigenomics and genomics to understand the causal pathways and mechanisms of how menarche and menopause modify breast cancer risk Shuai Li1, Graham Giles1-3, Melissa Southey,2-4 Roger Milne1-3, John Hopper1 Early menarche, late menopause and datasets from two cohort studies. pre-menopausal status are known to be associated with increased breast cancer This project aims to (1) screen DNA risk. methylation changes associated with age at menarche, age at menopause Understanding the causal pathways and and menopausal status by analysing mechanisms of how these risk factors genome-wide DNA methylation modify disease risk could provide datasets; (2) assess the evidence for evidence for breast cancer aetiology causality between DNA methylation and molecular targets for risk-reducing and the corresponding risk factor interventions. DNA methylation, an by applying and comparing the two epigenetic modification affecting causal inference methods, MR and ICE gene transcription and involved in FALCON; and (3) investigate whether carcinogenesis, can provide evidence for DNA methylation mediates the effects of causal pathways. the corresponding risk factor on breast cancer risk by assessing and comparing We have developed a novel causal both observational and genetic evidence. inference statistical method, ICE Preliminary results are expected at the FALCON (Inference about Causation from end of 2020. Examination of FAmiLial CONfounding), which gives the same causality Current Research Interests: conclusion as the commonly used Cancer epidemiology, genetic Mendelian randomisation (MR) with a epidemiology, epigenetic epidemiology. greater power. Both ICE FALCON and MR will be used to investigate the causal Keywords: pathways by integrating large-scale Breast cancer, menarche, menopause, genome-wide association study (GWAS) epigenetics, causal inference. and genome-wide DNA methylation 19  List of abstracts (continued) Dr Marlene Hao Co-lab head Institute: University of Melbourne Email address: : hao.m@unimelb.edu.au Grant funded by our principal supporter, The Can Too Foundation. A gut feeling about new therapies for glioma treatment: lessons from the enteric nervous system Marlene Hao1, Amelia Nash1, Thomas Gan1, Yvette Wilson1,2, Annette Bergner1, Lincon Stamp1 1. Department of Anatomy and Neursocience, the University of Melbourne, Australia. 2. Department of Physiology, the University of Melbourne, Australia Gliomas are an incredibly aggressive form and enteric glia. Our data shows that of brain cancer, making up the majority (70- these mice exhibit severe behavioural 80%) of malignant primary brain tumours. defects, including loss of co-ordination, dragging of hindlimbs, and irregular gait. Although there have been improvements Gross morphological analysis of the brain in diagnostic and therapeutic options, showed that they had gliomas of the survival rates remain low for brain cancers, optic nerves, which is typical of gliomas with only 1 in 5 patients surviving beyond derived from oligodendrocytes. However, 5 years. no tumours have yet been identified in the gut (n = 3). We are currently continuing Gliomas can arise from mutations that to characterise these mice, and plan to affect glial cells in the brain. Glial cells use RNA-sequencing to compare gene are found throughout the nervous system, expression differences between enteric including in the enteric nervous system, a glia and CNS glia isolated from this mutant network of neurons and glia located within model. We aim to identify candidate genes the wall of the gut. Gliomas in the gut are that are differentially regulated in mutant very rare, and over 95% of tumours are enteric glia that reduce their proliferative benign. These are very different from the and metastatic potential. malignant gliomas of the brain. Therefore, what is unique about enteric glial cells Current Research Interests: that protect them from developing Our laboratory has extensive experience in aggressive cancers? We hypothesise that studies of the enteric nervous system, with this protective effect could arise due to (i) experience in live calcium imaging, electro- activation of cell intrinsic pathways, or (ii) physiology, as well as stem cell biology and as a result of cell-cell interactions in the transplantation. We are novices in cancer gut environment. biology research and welcome this opportunity to learn more from the To investigate this, we have developed experienced researchers in this field! a novel strain of mice, Sox10-creERT2; Pik3caH1047R,Ptenfl/fl,R26R-YFP Keywords: mice, with mutations in the PI3K Glioma, enteric glia, RNA-seq, (phosphoinositide 3 kinase) pathway in oligodendrocytes, PI3K pathway. both central nervous system (CNS) glia 20  List of abstracts (continued) Dr Niantao Deng Senior Research Officer Institute: Garvan Institute of Medical Research Email address: n.deng@garvan.org.au Grant funded by our principal supporter, the Can Too Foundation. Understanding breast cancer patients’ response to neoadjuvant chemotherapy at single-cell resolution 1. The Kinghorn Cancer Centre & Cancer Research Division, Garvan Institute of Medical Research, Sydney, Australia; 2. St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Australia; 3. Chris O’Brien Lifehouse, Sydney, Australia; Niantao Deng1.2, Mun Hui1,2,3, Kate Harvey1,2 , Jessica Yang1,2 , Alexander Swarbrick1,2 The use of neoadjuvant therapy (NAT) sequencing analysis. In the first pair of before surgery to render large tumours samples collected before and after NAT, operable in breast cancer (BC) is we have successfully profiled 5,705 increasingly common. and 2,370 cells respectively with mean number of reads above 25,000 reads However, only <30% of breast cancers per cell. Initial analysis shows different treated with neoadjuvant chemotherapy compositions of cell populations before would have a complete pathological and after treatment, with enriched response, which is the complete cancer-associated fibroblasts and disappearance of cancer cells following reduced epithelial cell populations. We treatment. Even with the addition of have now collected more than 5 pairs of immunotherapy, the best response samples and in the process of sequencing is only 60%. Although generally safe, more samples. The data will provide immunotherapy can result in irreversible insights into understanding of breast organ damage in a small population of cancer microenvironment and their role in patients. We have developed a novel the patients’ treatment response. sequencing method to study a unique clinical cohort to understand mechanisms Current Research Interests: of treatment resistance in all breast Cancer genomics, bioinformatics, genome cancer subtypes. evolution. We have serial biopsy specimens from Keywords: breast cancer patients at diagnosis, Single cell sequencing, neoadjuvant during chemotherapy and at surgery. chemotherapy, complete pathological These samples are subsequently response, cell subpopulations. characterised through single-cell 21  List of abstracts (continued) Dr Jessica Holien Vice Chancellor’s Fellow Institute: RMIT University Email address: jessicaholien@outlook.com Grant funded by Cure Cancer through the Cancer Australia Priority-driven Cancer Support Scheme. Network informed analysis of Mucinous Ovarian Carcinoma (#179) 1. St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia 2. Peter MacCallum Centre, Melbourne, VIC, Australia 3. WEHI, Melbourne, VIC, Australia 4. Bio21 Institute, Melbourne, VIC, Australia 5. Baker IDI, Melbourne, VIC, Australia 6. RMIT, Melbourne, VIC, Australia Jessica Holien 1,6 , Samuel Lee 1 , Nathan Williams 1,6 , Yunkai Gao 2 , Dane Cheasley 2 , Matthew Wakefield 3 , Ian Campbell 2 , David Ascher4,5, Kylie Gorringe 2. Mucinous Ovarian Cancer (MOC) is a rare The interactions we discover may also be subtype that is highly distinctive from applicable to tumour types with related other ovarian carcinomas. key drivers, such as low-grade serous ovarian carcinoma and pancreatic cancer. Treatments that work well for other In addition, our approach can also be ovarian cancer subtypes are no more applied to established ovarian cancer likely to work for MOC than for any other genomic data sets, such as those for the tissue type. Indeed, MOC is intrinsically more common high-grade serous ovarian resistant to standard ovarian cancer carcinoma. chemotherapy (platinum/taxane). With the outcome for advanced stage patients Current Research Interests: being dire, any new effective therapy will Drug discovery, Protein-protein have a massive and immediate impact. interactions, networks, bioinformatics. We have leveraged our unique multi- Keywords: platform genomics data on MOC to Drug discovery, Protein-protein discover protein-protein interaction interactions, networks, bioinformatics. networks that offer a therapeutic opportunity. By incorporating protein structural elements into the analysis and computationally assessing the key protein-protein interactions for their druggability, we can conduct an effective therapeutic screening program which will readily translate to patients. 22  List of abstracts (continued) Dr Kelly Brooks Research Officer Institute: QIMR Berghofer Email address: Kelly.brooks@qimrberghofer.edu.au Grant co-funded with Cure Cancer, Cancer Australia and 50% funded by the Can Too Foundation. Investigating PARP inhibitors for the treatment of SF3B1 mutant melanomas 1. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 2. Cancer Research UK Manchester Institute, Manchester, United Kingdom. Kelly Brooks1, Richard Marais2, Nicholas Hayward1. Uveal melanoma (UM) is the most If this sensitivity can be validated and a common primary ocular cancer, and the direct mechanistic link demonstrated, it second most common melanoma subtype. is possible that PARPis could be readily repurposed and applied to SF3B1- Primary UM is effectively controlled withe mutant UM patients (15-24%) and other radiation, laser or surgical approaches, cancers with a significant proportion of including combinations of these. However, SF3B1-mutant cases including mucosal despite intervention at the stage of melanoma (MM) and chronic lymphoid primary disease, ~50% of UM cases leukaemia (CLL). will metastasize within 15 years, which is invariably fatal, with no effective Current Research Interests: treatments available. SF3B1 is a splicing Uveal Melanoma, Genetics, DNA Damage, factor that is mutated in ~20% of UM organotropism. and is associated with late metastatic progression, though its exact role, and the Keywords: impact of other UM-associated mutations Cancer biology, genetics, CRISPR. is unknown. Preliminary work suggests that these SF3B1 mutations sensitise these cancers to PARP inhibitors. 23  List of abstracts (continued) Dr Mark Adams Postdoctoral Research Fellow Institute: Institute of Health and Biomedical Innovation-Queensland University of Technology; Translational Research Institute Email address: mn.adams@qut.edu.au Grant supported by the Denton Trust. 1. Institute of Health and Biomedical Innovation Queensland University of Technology, Brisbane 2. Translational Research Institute, Brisbane Exploiting cell cycle factors to enhance chemotherapy response for non-small cell lung cancer patients Mark Adams1-2, Derek Richard1-2, Kenneth O’Byrne1-2 Lung cancer is the leading cause of improve response of NSCLC tumours CDCA3low NSCLC patients. This cancer-related mortality worldwide to therapy. strategy is being investigated for application in other solid malignancies. with a ~14% 5-year survival rate. The most commonly diagnosed form of this We demonstrate that in patients and in Ultimately, such a strategy might disease is non-small cell lung cancer. vitro analyses, CDCA3 levels correlate benefit cancer patient health outcomes by with measures of genome instability delaying or preventing therapy resistance. Chemotherapy employing platinum- and platinum sensitivity, whereby based doublet combinations remains CDCA3high tumours are sensitive to Current Research Interests: the cornerstone of treatment for cisplatin. In NSCLC, CDCA3 protein • Non-small cell lung cancer & breast non-oncogene driven NSCLC. This levels are regulated by the ubiquitin cancer (ER+ and triple-negative) treatment is commonly used in the ligase APC/C and c ...