Mucin-based targeted pancreatic cancer therapy

Abstract

The prognosis of pancreatic cancer (PC) patients is very poor with a five-year survival of less than 5%. One of the major challenges in developing new therapies for PC is the lack of expression of specific markers by pancreatic tumor cells. Mucins are heavily Oglycosylated proteins characterized by the presence of short stretches of amino acid sequences repeated several times in tandem. The expression of several mucins including MUC1, MUC4, MUC5AC, and MUC16 is strongly upregulated in PC. Recent studies have also demonstrated a link between the aberrant expression and differential overexpression of mucin glycoproteins to the initiation, progression, and poor prognosis of the disease. These studies have led to increasing recognition of mucins as potential diagnostic markers and therapeutic targets in PC. In this focused review we present an overview of the therapies targeting mucins in PC, including immunotherapy (i.e. vaccines, antibodies, and radioimmunoconjugates), gene therapy, and other novel therapeutic strategies.

Fig. (1). Immunotherapeutic strategies targeting mucins in PC

(A) Vaccination with Mucin-peptides or Mucin-pulsed dendritic cells enhances the activation of humoral and cell-mediated adaptive immune responses. Mucin-peptide loaded dendritic cell (DC) activate both CD4 T cells, which eventually leads to the activation of B cells to produce tumor-associated Mucin antibodies (i.e. humoral response), and CD8 T cells that target and kill Mucin-expressing tumors (i.e. cell-mediated response). (B) Tumor-associated Mucin antibodies are conjugated to radioactive isotopes or cytotoxic drugs to target and kill PC cells more efficiently.