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Pancreatic ductal adenocarcinoma (PDAC): clinical progress in the last five years
Osama M Mosalem1, Ahmed Abdelhakeem1, Nayef H Abdel-Razeq1
1Department of Medicine, Division of Hematology Oncology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL, USA.
Introduction:
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited therapeutic options and poor overall survival. In recent years, advances in genomic profiling have revealed the complex molecular and cellular heterogeneity of PDAC, offering new avenues for therapeutic intervention.
Areas Covered:
This review explores emerging therapeutic strategies targeting dysregulated molecular pathways, along with the tumor microenvironment, that have shown promise in overcoming drug resistance. Novel immunotherapy strategies, such as immune checkpoint inhibitors and CAR T-cell therapies, are currently being explored in an attempt to modulate PDAC immugnosuppressive microenvironment. Additionally, we highlight recent clinical trials over the last 5 years and innovative therapeutic strategies aiming to improve outcomes in PDAC.
Expert Opinion:
Significant progress in genomic profiling, targeted therapies, and immunotherapy is shaping the treatment of PDAC. Despite challenges posed by its dense stroma and immune suppressive microenvironment, novel strategies such as IL 6 and CD137 inhibitors, CAR-T, and therapeutic cancer vaccines are promising. KRAS targeted therapies are expanding beyond G12C inhibitors, with novel drugs in development that will further improve treatment options. Additionally, tumor treating fields (TTF) are being investigated in locally advanced PDAC, with the PANOVA-3 trial potentially integrating this modality into future treatment strategies. Continued advancements in these areas will significantly enhance PDAC outcomes.
Insights
New pancreatic cancer therapies target molecular pathways and the tumor microenvironment. Advances in immunotherapy, KRAS inhibitors, and tumor treating fields offer hope for improved patient survival.
Area of Science:
- Oncology
- Cancer Therapeutics
- Molecular Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with poor survival rates.
- Genomic profiling reveals PDAC's molecular and cellular heterogeneity, opening new therapeutic avenues.
Purpose of the Study:
- To review emerging therapeutic strategies for PDAC.
- To explore novel treatments targeting molecular pathways and the tumor microenvironment.
- To highlight recent clinical trials and innovative approaches for PDAC.
Main Methods:
- Review of recent scientific literature and clinical trials (last 5 years).
- Focus on targeted therapies, immunotherapy, and novel treatment modalities.
- Analysis of strategies to overcome drug resistance and the immunosuppressive tumor microenvironment.
Main Results:
- Advances in genomic profiling, targeted therapies, and immunotherapy are transforming PDAC treatment.
- Promising strategies include IL-6 and CD137 inhibitors, CAR-T cell therapy, and cancer vaccines.
- KRAS targeted therapies are expanding, and tumor treating fields (TTF) are under investigation.
Conclusions:
- Novel therapeutic strategies show promise in overcoming PDAC's challenges, including its dense stroma and immunosuppressive microenvironment.
- Continued advancements in targeted therapies, immunotherapy, and TTF are expected to significantly improve PDAC outcomes.
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