In vivo label-free optical signatures of chemotherapy response in human pancreatic ductal adenocarcinoma patient-derived xenografts

Autor: Jaena Park, Janet E. Sorrells, Eric J. Chaney, Amro M. Abdelrahman, Jennifer A. Yonkus, Jennifer L. Leiting, Heidi Nelson, Jonathan J. Harrington, Edita Aksamitiene, Marina Marjanovic, Peter D. Groves, Colleen Bushell, Mark J. Truty, Stephen A. Boppart
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Communications Biology, Vol 6, Iss 1, Pp 1-12 (2023)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-023-05368-y
Popis: Abstract Pancreatic cancer is a devastating disease often detected at later stages, necessitating swift and effective chemotherapy treatment. However, chemoresistance is common and its mechanisms are poorly understood. Here, label-free multi-modal nonlinear optical microscopy was applied to study microstructural and functional features of pancreatic tumors in vivo to monitor inter- and intra-tumor heterogeneity and treatment response. Patient-derived xenografts with human pancreatic ductal adenocarcinoma were implanted into mice and characterized over five weeks of intraperitoneal chemotherapy (FIRINOX or Gem/NabP) with known responsiveness/resistance. Resistant and responsive tumors exhibited a similar initial metabolic response, but by week 5 the resistant tumor deviated significantly from the responsive tumor, indicating that a representative response may take up to five weeks to appear. This biphasic metabolic response in a chemoresistant tumor reveals the possibility of intra-tumor spatiotemporal heterogeneity of drug responsiveness. These results, though limited by small sample size, suggest the possibility for further work characterizing chemoresistance mechanisms using nonlinear optical microscopy.
Databáze: Directory of Open Access Journals
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