Abstract P48: Advancing Personalized Anti-Cancer Pharmacotherapy: Magnetic Bioprinting of a Ductal Drug Screening Platform for Salivary Gland Mucoepidermoid Carcinoma

Abstract

Abstract Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the salivary glands (SG), and it arises from “reserve” stem cells within the ductal network. Recently, our research team has consistently generated acinar-like epithelial SG organoids using a magnetic three-dimensional bioprinting (M3DB) platform. However, 3D ductal constructs with lumenized and functional features have not been established by biofabrication strategies due to challenges related to the lack of epithelial polarity and reproducibility. Consequently, our research unit is developing an in vitro high throughput drug screening platform with bio-printed ductal constructs as avatars of MEC ductal units towards a more effective and personalized anti-cancer pharmacotherapy. M3DB, multiplex immunofluorescence, western blot, and functional assays were performed. M3DB induced the formation of ring-like organoid 3D constructs after the magnetic bioassembly of MEC HTB41 cells overnight. These bio-printed constructs had a lumen formation efficiency of ~70% and contained functional E-cadherin+ cell clusters expressing ZO-1 with mainly K14+ and K5+ ductal progenitor populations with high pro-mitotic activity (Ki-67). These bio-printed ductal-like constructs were then proteomic and functionally evaluated in the presence or absence of 5-fluorouracil (5-FU), a chemotherapy drug. Proteomic assessments revealed changes in cellular antioxidant response (Nrf2) as well as DNA damage repair (γ-H2AX) after 5-FU exposure, potentially safeguarding cells from damage and halting cancer cell cycle progression. Tumor cell invasion capabilities within co-culture in mili-fluidic platforms, and functional evaluation with cholinergic and adrenergic agonists and swelling assays confirmed the 5-FU-induced cytotoxicity, decreased invasion potential, and ductal hypofunction. In summary, our team successfully established novel bio-printed MEC ductal-like avatar platforms that will pave the way for personalized pharmacotherapy and precision oncology in SG malignant tumors. Citation Format: Yamin Oo, Tien T.T. Truong, Toan V. Phan, Khurshid Ahmed, Teerapat Rodboon, Risa Chaisuparat, Glauco R. Souza, Joao N. Ferreira. Advancing Personalized Anti-Cancer Pharmacotherapy: Magnetic Bioprinting of a Ductal Drug Screening Platform for Salivary Gland Mucoepidermoid Carcinoma [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P48.