Effective treatment of advanced metastatic disease remains the primary challenge in the management of inoperable
pancreatic cancer. Current
therapies such as
oxaliplatin (OxPt)-based
chemotherapy regimens (
FOLFIRINOX) provide modest short-term survival improvements, yet with significant toxicity.
Photodynamic therapy (
PDT), a light-activated
cancer therapy, demonstrated clinical promise for
pancreatic cancer treatment and enhances conventional
chemotherapies with non-overlapping toxicities. This study investigates the capacity of neoadjuvant
PDT using a clinically-approved
photosensitizer, benzoporphyrin derivative (
BPD, verteporfin), to enhance OxPt efficacy in metastatic
pancreatic cancer. Treatment effects were evaluated in organotypic three-dimensional (3D) cultures, clinically representative models that bridge the gap between conventional cell cultures and in vivo models. The temporally-spaced, multiparametric analyses demonstrated a superior efficacy for combined PDT+OxPt compared to each monotherapy alone, which was recapitulated on different organotypic
pancreatic cancer cultures. The therapeutic benefit of neoadjuvant
PDT to OxPt
chemotherapy materialized in a time-dependent manner, reducing residual viable tissue and
tumor viability in a manner not achievable with OxPt or
PDT alone. These findings emphasize the need for intelligent combination
therapies and relevant models to evaluate the temporal kinetics of interactions between mechanistically-distinct treatments and highlight the promise of
PDT as a
neoadjuvant treatment for disseminated
pancreatic cancer.