Item Details

title

Cancer Associated Fibroblast Chemosensitivity in an Appendiceal Cancer Organoid Model

author

Laney, Preston

abstract

Modeling disease is an important challenge for research, including for rare cancers. Traditional medical research in 2D in vitro culture of tissue has limited potential for applications due to cells displaying behavior different from that in vivo. Organoids are a novel technology which has shown promise in the accurate modeling of disease through recapitulating cellular spatial relationships which are not present in traditional 2D culture. Using organoids to model cancer has been shown to be a viable and revolutionary achievement which produces tissue like behavior that cannot be replicated effectively in 2D, including the role of tumor supporting cells including cancer associated fibroblasts (CAFs). With organoids, the future of personalized medicine is also being pursued with therapeutic studies using patient derived tumor organoids showing promise in furthering high throughput, patient to patient treatment strategies.In this study, we sought to focus the cytotoxicity of drugs used clinically to treat appendiceal cancer and their action on CAFs in comparison to tumor cells. Appendiceal cancer tumor tissue was characterized and examined for the presence of CAF markers, as well as cancer stem cell activity using immunostaining, flow cytometry, magnetic cell sorting and culture techniques. Using organoids containing CAFs, the effectiveness of 5-FU based regimens as well as Cytoreductive Surgery/Hyperthermic Intraperitoneal Chemotherapy (HIPEC) simulation showed drug resistance comparable to clinical results, whereas tumor organoids were susceptible to cytotoxicity. A comparison of CAF organoid drug treatment results with that of heterogeneous tumor cell organoids that were fabricated shortly after surgery showed expected clinical response to treatment while CAFs demonstrated resistance to chemotherapeutic cytotoxicity. Future studies should focus on the specific mechanisms by which CAF and tumor organoids can confer drug resistance, and how chemical and mechanical interactions of CAFs and tumor cells are determinant of disease traits and behavior.

subject

Cancer

Fibroblast

Organoid

contributor

Soker, Shay (advisor)

Marini, Frank (committee member)

Murphy, Sean (committee member)

Miller, Lance (committee member)

date

2024-05-23T08:35:50Z (accessioned)

2024-05-23T08:35:50Z (available)

2024 (issued)

degree

Biomedical Science – MS (discipline)

identifier

http://hdl.handle.net/10339/109394 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis