Cancer is a leading cause of death worldwide with 1 in 6 deaths caused or linked to cancer. The evolving nature of cancers means that development of resistance to both conventional and targeted cancer therapies is common and this contributes to treatment failure. This emphasizes the need for the continued discovery and development of novel anti-cancer molecules and combinatorial therapies to effectively treat cancers and overcome drug resistance. In pre-clinical cancer drug discovery, following in vitro screening the current standard is the testing of promising novel drugs or therapeutic strategies in vivo in sentient animals, typically rodent models. Although this approach has been normal practice over past decades, the associated high costs, drug failure rate and ethics of testing in sentient animals indicates the need for alternative strategies. The chorioallantoic membrane (CAM) tumour xenograft in ovo model of a developing chick embryo has the potential to reduce unnecessary testing in sentient species. Whilst there are published studies using CAM tumour models to embryonic developmental day 18, the embryo is becoming sentient by this time. Up to embryonic day 14, the developing embryo is non-sentient and classified as non-protected and a 3Rs model. This MSc research aimed to utilise the 14-day model, which has recently been established at Huddersfield, for pre-clinical evaluation of novel molecules with in vitro anti-cancer activity and to develop and optimise methodology for a new cell lines and tumour types of interest. Cell line-derived in ovo tumour xenografts for triple-negative breast cancer cell line HCC1937 and non-small cell lung cancer cell line H460 were successfully generated and used to evaluate in-house novel molecules. ‘Zn-LBB’ treatment of HCC-1937 tumour xenografts resulted in a statistically significant 45% decrease in mean tumour weight and no effect on embryo viability providing the first evidence for this drug of in vivo efficacy. Other results included the generation of a new 14-day in ovo tumour model, for germ cell tumours from the cell line NT2/D1. This was used to show that inhibition of anti-apoptotic protein MCL1 in combination with cisplatin was more effective towards tumours than either treatment alone. These in vivo therapeutic outcomes in ovo indicate the value of this 14-day model for preclinical anti-cancer drug evaluation and in enabling proof-of-concept of in vivo efficacy quickly and in a 3Rs, cost effective manner.
| Date of Award | 29 Jun 2026 |
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| Original language | English |
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| Supervisor | Simon Allison (Main Supervisor) & Craig Rice (Co-Supervisor) |
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