Targeting the Microenvironment to Overcome Gemcitabine Resistance in Pancreatic Cancer.
Eileen S CarpenterNina G SteeleMarina Pasca Di MaglianoPublished in: Cancer research (2020)
Pancreatic cancer is characterized by an extensive and complex microenvironment, and is resistant to both chemotherapy and immune checkpoint blockade. The study by Principe and colleagues in this issue of Cancer Research proposes a combinatorial approach based on targeting the very mechanisms of resistance to gemcitabine, a commonly used chemotherapeutic agent. The authors show that gemcitabine treatment causes profound changes in the pancreatic cancer microenvironment, including elevated TGFβ signaling and immune checkpoint expression, as well as increased antigen presentation in tumor cells. Accordingly, they show that the combination of chemotherapy, TGFβ signaling inhibition, and immune checkpoint blockade effectively restores antitumor immunity and results in a significant survival benefit.See related article by Principe et al., p. 3101.
Keyphrases
- locally advanced
- stem cells
- rectal cancer
- squamous cell carcinoma
- transforming growth factor
- cancer therapy
- radiation therapy
- poor prognosis
- papillary thyroid
- intellectual disability
- drug delivery
- case report
- lymph node metastasis
- combination therapy
- epithelial mesenchymal transition
- free survival
- replacement therapy
- childhood cancer
- smoking cessation
- binding protein
- signaling pathway