Ex vivo human pancreatic cancer avatars; establishing a platform to evaluate chemotherapeutic sensitivity

Abstract Background A significant variation is observed in the response rate to chemotherapy amongst patients with pancreatic cancer. Current guidelines advocate treatment regimes based purely on the patient's level of fitness. Such an approach fails to acknowledge the individual's tumour biology. Our aim was to assess whether patient derived cancer avatars could be used to deliver personalised therapy. Methods Individual avatars were created from resected tumours and were cultured ex vivo either under novel perfusion culture conditions or conventional static culture. Serial assessment of avatar proliferation capacity and metabolic function was performed to determine viability over time. Avatars were treated with chemotherapy and treatment sensitivity was determined. Avatar response to chemotherapy was subsequently compared to the patient's response in order to determine whether the patient's avatar could predict a clinically meaningful response to therapy. Results Patient derived cancer avatars (n=13) were successfully cultured for 12 days ex vivo. Perfusion culture of avatars was associated with a preservation of proliferative capacity (p < 0.01), metabolic function (p < 0.01) and a reduction in apoptosis rates (p < 0.05) when compared to conventional static culture. Avatars were treated with Gemcitabine and different response rates were observed varying from treatment sensitivity to resistance. A positive correlation was noted between the avatar's response and the patient's clinical response whilst on adjuvant Gemcitabine therapy. Conclusions Patient derived cancer avatars provide a window of insight into the tumour's response to chemotherapy and may allow for a paradigm shift in the long-term survival rates for this disease.