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Attenuating PI3K isoforms in pancreatic cancer: Focus on immune PI3Kγ
C Basset1, J Guillermet-Guibert2
1Centre de recherches en cancérologie de Toulouse CRCT, Inserm UMR1037, Toulouse, France; Université Toulouse III Paul Sabatier, Toulouse, France; Laboratoire d'excellence LABEX TouCAN, Toulouse, France; Service d'anatomo-pathologie, IUCT-Oncopole, hopitaux de Toulouse, Toulouse, France.
Abstract:
Phosphoinositide 3-kinases PI3Ks are major drug targets in oncology. Their role is far from being completely understood in pancreatic ductal adenocarcinoma. Pancreatic cancer is a dismal disease with limited therapeutic options except for surgery. We highlight here two elegant works demonstrating the role of PI3Kγ in cancer-associated macrophages applied in particular to pancreatic tumors. These data open new avenues for the use of PI3K-targetting drugs in cancer as anti-stroma therapies. Amongst the classI PI3K isoforms, PI3Kγ and PI3Kδ, are highly expressed in immune cells. Isoform-specific or pan-class I PI3K inhibitors which target all classI PI3Ks could be used as a targeted therapy towards cancer cell signaling but also as immunotherapies. Research on immunoregulation of human pancreatic cancer by the other ubiquitous α- or β-isoforms of PI3K needs to be performed.
Insights
Phosphoinositide 3-kinases (PI3Ks) are key in pancreatic cancer, particularly PI3Kγ in tumor-associated macrophages. Targeting PI3Ks offers new anti-stroma and immunotherapy strategies for pancreatic ductal adenocarcinoma.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options.
- The role of phosphoinositide 3-kinases (PI3Ks) in PDAC is not fully understood.
- PI3Kγ and PI3Kδ are highly expressed in immune cells, suggesting roles in cancer immunity.
Purpose of the Study:
- To highlight the role of PI3Kγ in cancer-associated macrophages within pancreatic tumors.
- To explore PI3K-targeting drugs as potential anti-stroma therapies.
- To emphasize the need for research into PI3Kα and PI3Kβ in pancreatic cancer immunoregulation.
Main Methods:
- Review of recent studies on PI3Kγ in cancer-associated macrophages.
- Analysis of PI3K isoform expression in immune cells relevant to cancer.
- Discussion of therapeutic implications of PI3K inhibitors.
Main Results:
- PI3Kγ plays a significant role in cancer-associated macrophages in pancreatic tumors.
- PI3K inhibitors targeting class I isoforms offer dual potential as anti-cancer and immunotherapy agents.
- Current research focuses on PI3Kγ and PI3Kδ, with less known about PI3Kα and PI3Kβ in PDAC.
Conclusions:
- Targeting PI3Kγ in macrophages presents a novel therapeutic avenue for pancreatic cancer.
- PI3K inhibitors could be developed as anti-stroma therapies and immunotherapies for PDAC.
- Further investigation into PI3Kα and PI3Kβ roles in pancreatic cancer immunity is warranted.
