Pancreatic ductal adenocarcinoma (PDA) is the most common form of pancreatic cancer with a 5-year survival rate of around 10%. Over 80% of PDA patients are diagnosed at late stages when the tumor is locally advanced or metastasized, therefore do not qualify for surgery. Standard chemotherapy, such as Gemcitabine alone or in combination with Abraxane has long been the standard of care for PDA. However, it provides only modest survival benefits since a large percentage of patients are either intrinsically resistant or develop resistance soon after treatment starts. Immune checkpoint blockade has achieved significant therapeutic success for a subset of cancer patients. Unfortunately, single agent immunotherapy has been ineffective in PDA. The reasons for this failure are complex, and likely stem from the nature of the stroma-rich tumor microenvironment in PDA. Therefore, there is an urgent need for the development of novel therapeutic strategies for PDA patients.
The advent of next-generation sequencing technology and large-scale tumor molecular profiling has shed light on the heterogeneity in human pancreatic cancer cells, as well as the heterogeneous stroma microenvironment and immune infiltration both across and within tumors. Tumor heterogeneity occurs at the genetic, epigenetic, proteomic and metabolomic levels. The stromal and immune compartments are linked by a web of interactions that promotes immune evasion and contributes to the onset and progression of pancreatic carcinogenesis, affecting cell plasticity, metastasis, chemo-resistance and radiotherapy-resistance. Based on these considerations, it is important to understand the variety and individual differences in pancreatic cancer and immune response for future development of diagnostic, therapeutic and prognostic strategies, including translational studies and clinical trials for personalized immunotherapy , prognostic assessment or risk assessment of distant metastasis.
This Research Topic aims to provide a comprehensive overview of recent advances in the association between tumor heterogeneity, disease evolution and therapeutic responses in pancreatic cancer. We welcome the submission of Review and Original Research articles covering basic, translational and clinical studies focusing on but not limited to, the following topics:
-Therapeutic harnessing of tumor heterogeneity in pancreatic cancer: novel targets and response biomarkers.
-Novel molecular mechanisms connecting intra- or inter-tumor heterogeneity with anti-cancer therapy responses in pancreatic cancer.
-Clinical implications of tumor heterogeneity in pancreatic cancer and clinical trials targeting stromal and/or immune components of pancreatic cancer
-Molecular mechanisms and therapeutic implications of the spatial architecture of pancreatic cancer: barrier or opportunity?
-Exploring and exploiting pancreatic cancer heterogeneity for disease diagnosis and staging.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Pancreatic ductal adenocarcinoma (PDA) is the most common form of pancreatic cancer with a 5-year survival rate of around 10%. Over 80% of PDA patients are diagnosed at late stages when the tumor is locally advanced or metastasized, therefore do not qualify for surgery. Standard chemotherapy, such as Gemcitabine alone or in combination with Abraxane has long been the standard of care for PDA. However, it provides only modest survival benefits since a large percentage of patients are either intrinsically resistant or develop resistance soon after treatment starts. Immune checkpoint blockade has achieved significant therapeutic success for a subset of cancer patients. Unfortunately, single agent immunotherapy has been ineffective in PDA. The reasons for this failure are complex, and likely stem from the nature of the stroma-rich tumor microenvironment in PDA. Therefore, there is an urgent need for the development of novel therapeutic strategies for PDA patients.
The advent of next-generation sequencing technology and large-scale tumor molecular profiling has shed light on the heterogeneity in human pancreatic cancer cells, as well as the heterogeneous stroma microenvironment and immune infiltration both across and within tumors. Tumor heterogeneity occurs at the genetic, epigenetic, proteomic and metabolomic levels. The stromal and immune compartments are linked by a web of interactions that promotes immune evasion and contributes to the onset and progression of pancreatic carcinogenesis, affecting cell plasticity, metastasis, chemo-resistance and radiotherapy-resistance. Based on these considerations, it is important to understand the variety and individual differences in pancreatic cancer and immune response for future development of diagnostic, therapeutic and prognostic strategies, including translational studies and clinical trials for personalized immunotherapy , prognostic assessment or risk assessment of distant metastasis.
This Research Topic aims to provide a comprehensive overview of recent advances in the association between tumor heterogeneity, disease evolution and therapeutic responses in pancreatic cancer. We welcome the submission of Review and Original Research articles covering basic, translational and clinical studies focusing on but not limited to, the following topics:
-Therapeutic harnessing of tumor heterogeneity in pancreatic cancer: novel targets and response biomarkers.
-Novel molecular mechanisms connecting intra- or inter-tumor heterogeneity with anti-cancer therapy responses in pancreatic cancer.
-Clinical implications of tumor heterogeneity in pancreatic cancer and clinical trials targeting stromal and/or immune components of pancreatic cancer
-Molecular mechanisms and therapeutic implications of the spatial architecture of pancreatic cancer: barrier or opportunity?
-Exploring and exploiting pancreatic cancer heterogeneity for disease diagnosis and staging.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.