Locoregional Therapies and Remodeling of Tumor Microenvironment in Pancreatic Cancer

Abstract

Despite the advances made in treatment, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal, even in the locoregional and locally advanced stages, with high relapse rates after surgery. PDAC exhibits a chemoresistant and immunosuppressive phenotype, and the tumor microenvironment (TME) surrounding cancer cells actively participates in creating a stromal barrier to chemotherapy and an immunosuppressive environment. Recently, there has been an increasing use of interventional radiology techniques for the treatment of PDAC, although they do not represent a standard of care and are not included in clinical guidelines. Local approaches such as radiation therapy, hyperthermia, microwave or radiofrequency ablation, irreversible electroporation and high-intensity focused ultrasound exert their action on the tumor tissue, altering the composition and structure of TME and potentially enhancing the action of chemotherapy. Moreover, their action can increase antigen release and presentation with T-cell activation and reduction tumor-induced immune suppression. This review summarizes the current evidence on locoregional therapies in PDAC and their effect on remodeling TME to make it more susceptible to the action of antitumor agents.

Nanoscintillator Coating: A Key Parameter That Strongly Impacts Internalization, Biocompatibility, and Therapeutic Efficacy in Pancreatic Cancer Models

“…To this end, stereotactic body radiotherapy (SBRT) has shown promising results for PDAC, enabling good tumor control and increasing life expectancy compared to chemotherapy alone or to chemotherapy combined with conventional RT. [ 5,9,10 ] However, as SBRT occasionally induces high toxicity, [ 11 ] other approaches are needed to improve the dose contrast between tumor and healthy tissue. One strategy is to accumulate high‐Z elements in the tumor before irradiation to induce the so‐called radiation dose‐enhancement (RDE) effect.…”

Emerging Therapeutic Options in Pancreatic Cancer Management

“…CAFs in PDAC are most often divided into three subtypes, with different tumor-supporting capacities: myofibroblast-type CAFs (myCAFs), inflammatory CAFs (iCAFs), and antigen-presenting CAFs (apCAFs) [11][12][13]. Local approaches such as radiation therapy, hyperthermia, microwave or radiofrequency ablation, irreversible electroporation, and high-intensity focused ultrasound are capable of modifying the tumor microenvironment (TME) and ECM composition and structure, potentially enhancing chemotherapy [14]. Recently, immunotherapy has become a novel and promising alternative approach to target tumors [15][16][17].…”