Lymphatic metastasis is the major metastatic pattern of pancreatic cancer and considered as an independent risk factor of survival. However, there is still no effective way for the diagnosis and treatment for lymphatic metastases of pancreatic cancer. In this study, using albumin as a carrier of gemcitabine (Gem), further modified by pyropheophorbide-a, we have designed and synthesized a nanoparticle (NP) compound named “pheophorbide-a (P@)-Gem-human serum albumin (HSA)-NPs”. By utilization of its tracer ability of lymphatic metastases, which is triggered by near-infrared irradiation and its visible dying ability, the compound is used for drug delivery tracking, meanwhile as a treating drug, as well as the combined effect of photodynamic therapy and chemotherapy. By the nude mice model of lymphatic metastases of pancreatic cancer (BxPC-3-LN7), we aim to explore the feasibility, effectiveness, and biological safety of diagnosis and treatment for the lymphatic metastases of pancreatic cancer by P@-Gem-HSA-NP, thereby, providing new methods and strategies for the study of nanodrug carrier and research on lymphatic metastases of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide, and the mortality of patients with PDAC has not significantly decreased over the last few decades. Novel strategies exhibiting promising effects in preclinical or phase I/II clinical trials are often situated in an embarrassing condition owing to the disappointing results in phase III trials. The efficacy of the current therapeutic regimens is consistently compromised by the mechanisms of drug resistance at different levels, distinctly more intractable than several other solid tumours. In this review, the main mechanisms of drug resistance clinicians and investigators are dealing with during the exploitation and exploration of the anti-tumour effects of drugs in PDAC treatment are summarized. Corresponding measures to overcome these limitations are also discussed.

Pancreatic cancer is a uniformly lethal malignancy with an abundant dense desmoplastic stroma. Because of its dense stroma, conventional drugs were considered to not penetrate this physical barrier, and this caused a systemic drug resistance. Thus, abolishing this barrier with targeted agents is considered to improve the efficiency of chemotherapeutic treatment. The Hedgehog (Hh) signaling pathway is a critical regulator of pancreas development and plays diversified roles in pancreatic cancer stroma and neoplastic cells. Increasing Hh expression in neoplastic cells added desmoplastic stroma accumulation in orthotopic tumors, and Hh inhibitors that target the stroma have an ability to prolong the overall survival of Pdx-1-Cre/KrasG12D/p53R172H mice models via deleting the stromal components and increasing vascularity in pancreatic tumor. However, the failure of translation from bench to bedside indicate the complexity of the relationship between Hh signaling and desmoplastic stroma, and more insights into the complex relationships between Hh signaling pathway and stroma, even tumor cells, might help redesign Hh-targeted therapy. In this review, we discuss the possible mechanism of translation of Hh inhibitor in the clinic from pathology to molecular mechanism.

Hepatic resection is a safe procedure; furthermore, it is worth doing such an extended surgery for PDAC patients due to additional survival benefit in the medium-term (less than 3 years). However, further randomized, controlled trials are urgently needed.