WEHI PhD Completion Seminar hosted by Associate Professor Oliver Sieber

EunJun Li

PhD Student – Sieber Laboratory, Personalised Oncology division – Cancer Research & Treatments Theme, WEHI

Novel approaches for optimizing drug treatments for patients with colorectal cancer

Davis Auditorium

Join via TEAMS

Including Q&A session

CRC is a common malignancy and the second most common cause of cancer-related death worldwide. CRCs are highly heterogeneous at the molecular and clinical level, and current treatments have limited efficacy with most metastatic tumours developing treatment resistance. Drug combination therapy offers an opportunity to enhance therapeutic responses. Drug repurposing is an efficient way to save time, cost, and reduce safety risk for drug development by investigating of existing drugs for new therapeutic purposes.

Around 70% of sporadic colorectal cancer exhibits chromosomal instability. Aneuploidy is a consequence of chromosome instability and the presence of aneuploidy in CRC is associated with an increased risk of metastatic progression and poorer disease outcomes. However, the underlying mechanisms and specific genes responsible for the various levels of aneuploidy are still unknown.

During my PhD, I performed validation screens of candidates from a high-throughput drug combination screen which aimed to identify novel synergistic drug combinations utilising existing agents in combination with standard-of-care CRC chemotherapeutics (5-FU, SN-38 and Oxaliplatin). I validated the top 8 hits on 32 CRC cell lines and was able to identify 4 strong candidates that worked synergistically with the standard-of-care CRC chemotherapeutics to promote cancer cell death. I further investigated the molecular mechanisms and in vivo efficacy of 2 candidates. For my second project, I generated a MACROD2 and p53 mouse model and explored the impact of MACROD2 and p53 alterations on intestinal tumor development and CIN-driven aneuploidy.

All welcome!