Low-dose X-ray irradiation combined with FAK inhibitors improves the immune microenvironment and confers sensitivity to radiotherapy in pancreatic cancer

Biomed Pharmacother. 2022 Jul:151:113114. doi: 10.1016/j.biopha.2022.113114. Epub 2022 May 17.

Abstract

Radiation therapy offers limited clinical benefits for patients with pancreatic cancer, partly as a result of the predominantly immunosuppressive microenvironment characteristic of this specific type of cancer. A large number of abnormal blood vessels and high-density fibrous matrices in pancreatic cancer will lead to hypoxia within tumor tissue and hinder immune cell infiltration. We used low-dose X-ray irradiation, also known as low-dose radiation therapy (LDRT), to normalize the blood vessels in pancreatic cancer, while simultaneously administering an inhibitor of focal adhesion kinase (FAK) to reduce pancreatic cancer fibrosis. We found that this treatment successfully reduced pancreatic cancer hypoxia, increased immune cell infiltration, and increased sensitivity to radiation therapy for pancreatic cancer.

Keywords: FAK; Immune microenvironment; Low-dose X-ray irradiation; Pancreatic cancer; Radiosensitivity.

MeSH terms

  • Carcinoma, Pancreatic Ductal* / pathology
  • Carcinoma, Pancreatic Ductal* / radiotherapy
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors
  • Focal Adhesion Protein-Tyrosine Kinases / therapeutic use
  • Humans
  • Hypoxia
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / radiotherapy
  • Tumor Microenvironment* / immunology
  • X-Ray Therapy* / methods

Substances

  • Focal Adhesion Protein-Tyrosine Kinases