Friday, 10th February 35th Lorne Cancer Conference 2023

• Mechanisms of cell plasticity in breast cancer  - Celine Vallot
• State-gating cancer: a new therapeutic strategy to prevent and treat chemotherapy-resistant disease    - Christine Chaffer
• Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment - Marija Dinevska
• Loss of a growth arrest and DNA-damage inducible protein promotes resistance to a new form of cell death in leukaemia   - Nunki Hassan
• Heterogeneity of acquired resistance in ovarian cancer - Elizabeth Christie

• Mapping of the molecular interactions between leukemia, inflammation and the immune system - Iannis Aifantis
• Ceramide-induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia  - Stuart Pitson
• Heme biosynthesis regulates gene expression, cell fate and drug response in acute myeloid leukaemia - Lev Kats
• Second messenger signalling influences the kinome and methylome of kinase-activated paediatric acute myeloid leukemia. - Zacary P Germon
• Modelling treatment response and disease progression in Jak2-mutant myeloproliferative neoplasms  - Megan Bywater

Don’t miss this one-hour scientific workshop to find out how BGI oncology solutions are empowering in Australia’s leading cancer research. The workshop features two guest speakers: Dr. Dmitrii Shek, Westmead Institute for Medical Research, will be presenting a cohort study on genomic alterations and in-depth mutation analysis in metastatic thoracic tumour tissues and immune-checkpoints inhibitors, and A/Prof. Simon Chu, Research Group Head, Hudson Institute of Medical Research, will be sharing his expertise in ovarian cancer research and his latest findings on identifying mutational landscape of ovarian granulosa cell tumours to predict and/or drive late recurrence and/or aggressive behaviour to develop effective targeted personalised therapeutic options for patients using both RNASEQ and Whole Exome Sequencing. Save your seat at this link.

Comparative skin cancer atlas and interactome: A multi-modal spatial approach to uncovering the cells  and interactions underlying skin cancer diversity

Quan Ngyuen – University of Queensland

NHMRC Emerging Leadership Fellow, Centre for Genetics and Population Health, Institute for Molecular Bioscience
Affiliate Senior Research Fellow, School of Biomedical Sciences, Faculty of Medicine

The three major skin cancer types - squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma - account for >70% of all cancer. Although these cancers all derive from the outer skin layer (epidermis), variability in cell type composition and interactions causes substantial cross-cancer differences in disease initiation and invasive and metastatic potential. A knowledgebase of cell type composition and cell-to-cell interactions within the three skin cancers is needed to aid the assessment of risks and prognosis upon patient presentation. Here we integrated six distinct yet complementary spatial single-cell technologies to build the largest cell atlas and interactome of SCC, BCC, and melanoma to date.

First, we performed single-cell RNA sequencing (scRNAseq) on >50,000 cells from 11 paired healthy and SCC patient biopsies. We found 30 molecularly-distinct cell types/states, 18 of which were significantly enriched in SCC tissues and expressed strong transcriptional signatures of pro-tumour signalling. GeoMx spatial proteomics data independently validated the presence of rare immune cell types defined by scRNAseq. Visium and CosMx transcriptomic analyses were performed for all three skin cancer types to map spatial neighbourhoods and construct a cell-to-cell interaction atlas. We screened all captured ligand-receptor (LR) pairs in 121 possible cell type combinations to reveal signalling between cancer types/states, patients, and tissue regions.

With CosMx data, we found between 2-12 LR pairs specific to each cancer type, some of which have been previously implicated in skin cancer progression and metastasis. We independently validated two key LR interactions, PD1_PDL1 and IL34_CSF1R, using Opal Multiplex Polaris and RNAscope data. Downstream analysis of IL34_CSF1R signalling zones suggested enrichment of IL34-related antigen presenting pathways in melanoma. Overall, we present a valuable database and analysis approaches to reveal potential biomarkers of initiation and progression of the most lethal type (melanoma) and the most common types (SCC and BCC) of skin cancer. This resource is available for users to explore interactively at the skInteractive web browser: https://skincspatialatlas.web.app/ 

Oncofetal Ecosystem in HCC: Towards Spatial Precision Oncology

Ankur Sharma Ph.D. - Laboratory Head - Harry Perkins Institute of Medical Research. Senior Research Fellow – Curtin University

Embryonic development is characterized by rapidly dividing cells, cellular plasticity and a highly vascular microenvironment. These features are similar to those of tumour tissue in that malignant cells are characterized by their ability to proliferate and exhibit cellular plasticity. The tumour microenvironment also often includes immunosuppressive features. Reciprocal communication between various cellular subpopulations enables fetal, and tumour tissues to proliferate, migrate and escape immune responses. Fetal-like reprogramming has been demonstrated in the tumour microenvironment, indicating extraordinary cellular plasticity and bringing an additional layer of cellular heterogeneity. In this talk, I will share insights from NanoString's SMI platform CosMx in identifying an oncofetal niche in tumour tissue and its implication in therapy response.

• NK cells: next generation cell therapies for cancer - Katy Rezvani
• METTL3 inhibition enhances anti-tumour immunity by way of a cell-intrinsic interferon response   - Andrew A Guirguis
• Time: a forgotten dimension in cancer immunotherapy - Rachael Zemek
• Pervasive HLA disruption in lung cancer evolution - Clare Puttick
• Heterogeneity and function of mammary gland fibroblasts - Rosa Pascual
• Temporal proteomic profiling reveals Nidogen-2 as a new stromal co-target in pancreatic cancer - Brooke Pereira
• CRISPR-directed chromosomal translocations provide novel insights into leukaemia initiation - Teresa Sadras
• Sensitivity to immune-mediated stress as a novel avenue in leukaemia immunotherapy - Basit Salik
• A novel approach to the treatment of T-cell acute lymphoblastic leukaemia using the AKR1C3-activated prodrug, ACHM-025 - Cara E Toscan
• The epigenetic basis of synergy in combining CDK4/6 inhibition and endocrine therapy in breast cancer - April C Watt
• Investigating the role of Peroxidasin, an extracellular matrix protein, in cancer progression and metastasis - Kaitlin Wyllie

Includes flash talk presentations. 

Rosa Pascual
Heterogeneity and function of mammary gland fibroblasts abs# 30

Brooke Pereira
Temporal proteomic profiling reveals Nidogen-2 as a new stromal co-target in pancreatic cancer abs# 31

Teresa Sadras
CRISPR-directed chromosomal translocations provide novel insights into leukaemia initiation abs# 32

Basit Salik
Sensitivity to immune-mediated stress as a novel avenue in leukaemia immunotherapy abs# 33

Cara E Toscan
A novel approach to the treatment of T-cell acute lymphoblastic leukaemia using the AKR1C3-activated prodrug, ACHM-025 abs# 34

April C Watt
The epigenetic basis of synergy in combining CDK4/6 inhibition and endocrine therapy in breast cancer abs# 35

Kaitlin Wyllie
Investigating the role of Peroxidasin, an extracellular matrix protein, in cancer progression and metastasis abs# 36

• Investigating NDRG1 as a candidate biomarker in Breast cancer Brain Metastasis   - Vaibhavi Joshi
• Interrogating the cell-of-origin of BRCA2 mutant breast cancer to identify novel targets for chemoprevention - Rachel Joyce
• Understanding the regulation of the pro-apoptotic BH3-only protein PUMA to enhance the efficacy of cancer treatment - Deeksha Kaloni
• Kisspeptin promotes mesenchymal-like transition via proteomic regulation of transcription factors and classical markers in KISS1R-expressing Glioblastoma - MUHAMAD NOOR ALFARIZAL KAMARUDIN
• Characterizing the tumour microenvironment in multiple primary cancers - Imalki Kariyawasam
• Targeted delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment of high-risk childhood leukemia - Maria Kavallaris
• Genetic Manipulation of Organoids to Investigate the Role of Mutant TP53 in Cancer - Lois Kerswell
• Choice of antibody is critical for specific and sensitive detection of androgen receptor splice variant-7 in circulating tumour cells - Tanzila Khan
• Using CRISPR base editing applications to accurately identify tumour promoting mutations in lymphomagenesis. - Christina Koenig
• Spatially resolved proteomics to identify cellular communication networks in pancreatic cancer - Clara Kosasih
• Developing microenvironment-based prognostic biomarkers for early breast cancer - Christina Kozul
• Targeting the urokinase plasminogen activator (uPA) inhibits cell-surface plasmin turnover and metastasis in pancreatic ductal adenocarcinoma: A preclinical drug target validation study - Ashna A Kumar
• UHRF1/UBE2L6/UBR4-mediated ubiquitination regulates EZH2 abundance and thereby melanocytic differentiation phenotypes in melanoma - Gamze Kuser Abali
• Codon-biased changes in the proteome in response to modulation of Uridine 34 tRNA modifications impair the growth of prostate cancer cells - Eric P Kusnadi
• Cell intrinsic determinants of acute leukaemia relapse following CAR T cell therapy - James A Kuzich
• Investigating copy number signatures as biomarkers of therapeutic vulnerabilities in high-grade serous ovarian carcinoma - Elizabeth Kyran
• Characterising the role of ARRDC3 as a regulator of P53-mediated apoptosis - Eddie La Marca
• Development of a novel syngeneic mouse model   - Maria Lambouras
• Subcellular specific targeting of JNK as a novel anti-metastatic therapy in triple negative breast cancer - Sharissa Latham
• PURPLE translational registry: A novel multi-sided platform approach to accelerate research in pancreatic cancer - Belinda Lee
• Comparing histological and clinical measures of photodamaged in skin close to and distant from a prior melanoma - Katie J Lee
• A Multi-Omic Approach to Unravel How PRMT5 inhibitor (GSK3266595) Inhibits Pancreatic Ductal Adenocarcinoma Proliferation - Michael KC Lee
• Mutational variants and immune infiltrates in early colorectal polyps - Jun Li
• High preoperative levels of circulating SFRP5 predict better prognosis in colorectal cancer patients - Runhao Li
• Using new gene reporter mice and RNAseq analysis to uncover how p53 determines different cellular fates – cell death vs cell cycle arrest - Elizabeth Lieschke
• Investigating upstream open reading frames that regulate gene expression during stress - Chun Shen Lim
• A Semi-Automated Workflow for High-Throughput Phosphoproteomics Analysis of Clinical Samples - Terry Lim Kam Sian
• Inhibiting PRMT5: A Novel Target for the Treatment of Melanoma  - Lydia Lim
• Primary dermal melanoma systematic review - Lawrence Lin
• Targeted reprogramming of aggressive prostate cancer towards a benign transcriptional state - Natalie Lister
• Systematic loss of function screens identify MAPK pathway specific functional circular RNAs - Ling Liu
• Leveraging the nucleolar DNA damage response in ovarian cancer therapy - Ruofei Liu
• The role of ADAM9 in the tumor microenvironment and as a potential target for cancer vaccine - Shih-Jen Liu
• Risk of developing skin cancers before and after solid organ transplant - Zhao Feng Liu
• Why does endocytosis inhibition lead to increased endosomal delivery of ADC’s: pharmacological reversal. - Benedict Lum
• Lymphopenia during lung cancer chemoradiotherapy is proportional to FLT-PET-detected suppression of irradiated marrow and has implications for adjuvant immunotherapy - Michael MacManus
• A rapid increase in ctDNA is detected at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC - Michael MacManus
• Circulating immune cells show immunomodulatory features that track the stages of metastatic breast cancer - Stefano Mangiola
• Studying the immune microenvironment in lung cancer patients using spatial multi-omic approaches - Claire Marceaux
• Targeting androgen signaling alongside standard care in glioblastoma - Sofia RE Mason
• Extracellular vesicles in cancer therapy - Suresh Mathivanan
• Uncovering novel functions of ZEB1 in triple-negative breast cancer   - Cerys McCool
• Expression of APOBEC genes in breast luminal progenitor cells - Conor F McGuinness
• Understanding the role of intraepithelial lymphocytes in colorectal cancer progression - Lisa Mielke
• An epigenetic atlas of mammary epithelial cells identifies regulators of lineage restricted expression - Michael Milevskiy
• SMAD4 restrains mTOR signalling to prevent oesophageal tumourigenesis - Julia Milne
• Using the CUP Prediction Algorithm (CUPPA) to inform clinical curation of whole genome and transcriptome sequencing of cancers of unknown primary - Camilla Mitchell
• Uncovering subtype specific intra-tumoural heterogeneity in brain cancer - Joel JD Moffet
• Improving the therapeutic outcome of PDAC by targeting copper-dependent lysyl oxidase using the copper chelator ATTM - Ellie Mok
• Activating programmed cell death pathways to improve therapy in glioblastoma multiforme (GBM) - Diane Moujalled
• Establishing functional drivers and novel therapeutic targets in oesophageal adenocarcinoma - Ebtihal Mustafa
• Desmoglein-2 as a regulator of Pancreatic Ductal Adenocarcinoma progression - Kay Myomin
• Mathematical Modelling of Aptamer Transport across the Blood-Brain Barrier and its Distribution in Brain Aiming for Tumour Treatment - Maryam Nakhjavani
• Targeting clinically relevant lncRNAs identified from TCGA datasets to reduce TMZ resistance in GBM through shotgun proteomics - Prakrithi Narayanan
• Phenotypic and functional characterisation of macrophages in early breast cancer - Ibraheem Nasir
• Investigating the genetic profile of low grade serous ovarian carcinoma - Chloe Neagle
• BRCA1 secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance - Ksenija Nesic
• Systematic loss of function screens identify SMAD2 dervied circRNA as a target for WNT/β-catenin dependent cancers - Matthew Neve
• Investigating the intra-tumoral heterogeneity of metastatic small cell lung cancer patient samples - Jin Ng
• Exploiting vulnerabilities to ferroptosis to treat metastatic oesophageal cancer  - Zoe Nguyen
• Curating germline variants identified by whole genome sequencing in the precision oncology context - Shannon R Nicolson
• The tumour immune microenvironment differs between anatomical locations in mesothelioma preclinical models - Lizeth Orozco Morales
• Delineating the time-dependent changes in both tumour cells and the immune microenvironment upon upfront and sequencing of targeted- and immuno-therapy   - Riyaben P Patel
• Exploring the mitochondrial-epigenetic axis in a stem cell differentiation model - Vibha Patil
• Rationalising the use HDAC inhibitors for primary and relapsed neuroblastoma through a single-cell analysis of chemoresistance - Monica MP Phimmachanh
• Spatial lncRNA signatures in colorectal cancer   - Holly R Pinkney
• Characterising gene co-expression changes facilitating the loss of features of multicellularity driving Prostate cancer progression - Mikhail Dias
• Distinct assemblies of heterodimeric cytokine receptors govern stemness programs in leukaemia - Winnie L Kan