Emerging applications of cancer bacteriotherapy towards treatment of pancreatic cancer

Abstract

Pancreatic cancer is a highly aggressive form of cancer with a five-year survival rate of only ten percent. Pancreatic ductal adenocarcinoma (PDAC) accounts for ninety percent of those cases. PDAC is associated with a dense stroma that confers resistance to current treatment modalities. Increasing resistance to cancer treatments poses a challenge and a need for alternative therapies. Bacterial mediated cancer therapies were proposed in the late 1800s by Dr. William Coley when he injected osteosarcoma patients with live streptococci or a fabrication of heat-killed Streptococcus pyogenes and Serratia marcescens known as Coley’s toxin. Since then, several bacteria have gained recognition for possible roles in potentiating treatment response, enhancing anti-tumor immunity, and alleviating adverse effects to standard treatment options. This review highlights key bacterial mechanisms and structures that promote anti-tumor immunity, challenges and risks associated with bacterial mediated cancer therapies, and applications and opportunities for use in PDAC management.

Group A streptococcal collagen-like protein 1 restricts tumor growth in murine pancreatic adenocarcinoma and inhibits cancer-promoting neutrophil extracellular traps

“…GAS and other bacteria are attractive candidates for cancer therapy in their capabilities to be recognized by immune cells even in immunosuppressive tumor environments ( 8 ). This recognition has the capacity to switch this “immunologically cold” environment to a more immunostimulatory one ( 57 ).…”

“…Though his work fell out of favor with implementation of radiation and chemotherapy, evidence suggests Coley’s intuition of stimulating the immune system to elicit an anti-cancer response is effective ( 7 ). Bacteria harbor a variety of structures, toxins and mechanisms that make them attractive candidates as therapeutic agents with some evidence of preclinical efficacy in PDAC ( 8 ). Evidence suggests that group A Streptococcus (GAS) peptides ( 9 ) and superantigens ( 10 ) can elicit tumor regression.…”

Group A Streptococcal Collagen-like Protein 1 Restricts Tumor Growth in Murine Pancreatic Adenocarcinoma and Inhibits Cancer-Promoting Neutrophil Extracellular Traps

“…GAS and other bacteria are attractive candidates for cancer therapy in their capabilities to be recognized by immune cells even in immunosuppressive tumor environments [8] . This recognition has the capacity to switch this immunologically "cold" environment to a more immunostimulatory one [51] .…”

“…Though his work fell out of favor with implementation of radiation and chemotherapy, evidence suggests Coley's intuition of stimulating the immune system to elicit an anti-cancer response is effective [7] . Bacteria harbor a variety of structures and mechanisms that make them attractive candidates as therapeutic agents with some evidence of preclinical efficacy in PDAC [8] . Evidence suggests that group A Streptococcus (GAS) peptides [9] and superantigens [10] can elicit tumor regression.…”