Translational Oncology Research Laboratory
2019 Translational Oncology group. L-R: 1st row - Dr Ashalyn Watt, Dr Sophia Frentzas, Prof Eva Segelov, Dr Sameer Greenall. 2nd row - Mr Timothy Chen, Dr Gwo Yaw Ho, Dr Edmond Kwan, Ms Annette McClellan
Unfortunately some cancer patients don’t respond or are resistant to therapy. Our research aims to find out why.
Focussing on the upper and lower gastrointestinal cancers, colorectal cancer, lung cancer and brain cancer, our laboratory seeks to understand how patient tumours respond to clinical therapies (such as immunotherapy, targeted therapy and chemotherapy), why patient tumours are able to resist clinical therapy, and discover biomarkers of response. Our ultimate goal is to use this new knowledge to improve clinical practise, more effectively treat patients and improve their survival and wellbeing.
Immunotherapy, ctDNA, Genomic adaptation, Immunological adaptation and response, Neoadjuvant therapies, Tumour immunogenicity
Meet the Translational Oncology Research Laboratory team.
See Pubmed link for recent publications.
- Clinical Genomics
- Australasian Gastro-Intestinal Trials Group (AGITG)
- Aspirin for Dukes C and High Risk Dukes B Colorectal Tumours (ASCOLT) Trial Group
Current Clinical Trials
- NCT00565708: Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers (ASCOLT) Trial. In this randomized, placebo-controlled adjuvant study, investigators will see if Aspirin in patients with dukes C or high risk dukes B colorectal cancer (ASCOLT) can improve survival in this patient population over placebo control.
- NCT03084770: Asymptomatic Small Pancreatic Endocrine Neoplasms (ASPEN) Trial. The aim of the study is to evaluate the most appropriate management of sporadic asymptomatic non-functioning pancreatic neuroendocrine neoplasms (NF-PNEN) ≤ 2 cm
- Rectal AveRec Neo Adjuvant Rectal ES FM
- Solid Tumour KX-012AX-002 Bioequivalence study of oral paclitaxel in patients treated with IV paclitaxel ES IN
- HREC/18/MonH/346: The role of dendritic cells (DCs) in non-small-cell lung carcinoma (NSCLC) patients receiving anti-PD-1 immunotherapy. This study will take sequential blood and tumour biopsies to monitor immunological tumour responses to immunotherapy.
in non-small-cell lung carcinoma (NSCLC) patients receiving anti-PD-1 immunotherapy
Immune-checkpoint inhibitors such as anti-PD-1 monoclonal antibodies have been trialled and proven successful in a number of cancers. Recently, it has been found that DCs up-regulate the immune checkpoint PD-1 in response to inflammatory stimuli as well as in the tumour microenvironment itself. This project aims to further recent knowledge acquired in lab based and animal projects by translating data in patients with NSCLC. In examining the effects of anti-PD-1 therapies on DCs greater understanding of anti-PD-1 mechanisms of action will be acquired, aiding in the identification of biomarkers to predict effectiveness of treatment.
Main contacts: Dr Maja Green, Prof Eva Segelov, Dr Sameer Greenall
Recent breakthroughs in therapies that reactivate the immune system attack against tumours, so called immunotherapy, hold great promise for improving patient survival. The antibodies nivolumab and pembrolizumab are immunotherapies that are approved for NSCLC and have resulted in revolutionary long-term durable responses in 25-30% of patients. However, a majority of patients either do not respond or relapse in the face of these agents, for reasons that are poorly understood. This project aims to conduct an array of genetic and immunological testing on a sequential patient sample cohort, taken from initiation of therapy to patient progression, of circulating tumour DNA (ctDNA), plasma and lymphocytes to discover definitive reason(s) that underpin(s) response and relapse to immunotherapy in NSCLC. Our goal is to identify these mechanisms to better stratify NSCLC patients for response to immunotherapy and identify vulnerabilities to be drugged in combination with anti-PD-1 agents to augment anti-tumour response.
Main contacts: Dr Sameer Greenall, Prof Eva Segelov
The ICECREAM (The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation) trial explored the use of cetuximab as a monotherapy, or in combination with irinotecan in patients with metastatic colorectal cancer (CRC) whose tumours had progressed on standard chemotherapy. The treatment groups did not display significant differences in terms of disease control, bringing into question the mechanisms of resistance. Animal data suggests that infiltration of dendritic cells is decreased in patients not responding to anti-EGFR antibodies. This project will investigate the expression levels and distribution of DCs in the primary tumour. Furthermore, we seek to investigate the expression levels of a panel of inflammatory cytokines in patient serum over time and treatment.
Main contacts: Prof Eva Segelov, Dr Maja Green, Mr Cameron Naidu
Colorectal cancer (CRC) is one of the most prevalent and deadly cancers. Studies have shown that neoadjuvant chemotherapy has significantly improved patient survival and complete pathological clearance in locally rectal cancers. This makes it an ideal setting for testing the efficacy of novel treatments. Large retrospective studies have shown significant reduction in CRC recurrence and death in patients who subsequently use aspirin. We have access to biospecimens from the large prospective international CRC adjuvant aspirin trial ASCOLT (Aspirin for Dukes C and High Risk Dukes B Colorectal Tumours). Verifying and expanding a biomarker profile for aspirin efficacy will allow selection of a subpopulation that will benefit from adjuvant aspirin, and spare others from aspirin associated toxicities. A large retrospective study demonstrated adjuvant aspirin use was associated with longer CRC-specific survival in patients with low level PD-L1 expression. This project will use the biospecimens from the ASCOLT trial to validate the predictive utility of PD-L1 expression in determining benefit of adjuvant aspirin.
Main contacts: Prof Eva Segelov, Dr Maja Green
Following intensive radiation/chemotherapy treatments, the risk of recurrence of CRC is as high as 40%, which makes early detection of recurrence pivotal for early clinical intervention and prolonged survival. Current methods of early detection of recurrence are not optimal. A novel Australian invented ctDNA blood test (Colvera™ by Clinical Genomics) has been developed and validated, testing the presence of methylated BCTA and IKZF1 genes. These two genes, involved in cell cycle regulation and apoptosis, appear to play an important functional role in maintaining a healthy state in colorectal tissue. The aim of “Catcher” projects is to investigate the utility of the Colvera blood test in early detection of recurrence of colorectal cancers.
Main contacts: Dr Daphne Day, Prof Eva Segelov, Dr Maja Green
The emotional and financial impacts of a cancer diagnosis are often significant, and this study aims to assess how travel time may impact cancer care. Travelling can be a burden and within the Melbourne metropolitan area this is exacerbated as our major treatment hospitals are centralised while our population is spread further out. Built on the foundation laid by Professor Thanh Phan in his work on stroke, we will be using retrospective data with the Google Maps API to calculate travel time, finding the patients’ closest hospital to compare with where they were admitted for treatment. Though not as time-critical as stroke, cancer care could be optimised to reduce patient travel time and thus the burden of diagnosis. Mapping cancer incidence by postcode and incorporating hospital location will allow the optimal site for admission to be given for a particular postcode, while using google maps allows data such as traffic conditions to be incorporated.
Main contacts: Prof Eva Segelov, Dr Maja Green