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Advances in Novel Targeted Therapies for Pancreatic Adenocarcinoma
1Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Purpose:
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. Recent advances in targeted therapies have opened new avenues for intervention in PDAC, focusing on key genetic and molecular pathways that drive tumor progression.
Methods:
In this review, we provide an overview on advances in novel targeted therapies in pancreatic adenocarcinoma.
Results:
Here, we explore the latest development in targeting the KRAS pathway, a historically "undruggable" target crucial to PDAC pathogenesis. Strategies to inhibit KRAS include direct KRAS-targeted therapies, modulation of upstream and downstream signaling, KRAS-specific siRNA, and novel combination therapies integrating KRAS inhibitors with immune checkpoint blockade, PARP inhibitors, chemotherapy, CDK4/6 inhibitors, and autophagy modulators. Beyond KRAS, emerging targets such as NRG1 fusions, NTRK/ROS1 fusions, RET alterations, and the PRMT5/CDKN2A/MAT2A axis, along with EGFR and Claudin18.2 inhibitors, are also discussed as promising therapeutic strategies. Additionally, the review highlights novel approaches for microsatellite instability-high (MSIH) PDAC and emerging therapies, including adoptive cell therapies (CAR-T, TCR, TIL), cancer vaccines, and strategies to modify the tumor microenvironment.
Conclusion:
Overall, the rapid evolution of targeted therapies offers renewed optimism in the fight against pancreatic cancer, a malignancy with historically poor outcomes.
Insights
Novel targeted therapies are emerging for pancreatic ductal adenocarcinoma (PDAC), a deadly cancer. Research focuses on inhibiting the KRAS pathway and other molecular targets, offering new hope for patients with limited treatment options.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis.
- Limited therapeutic options exist for PDAC, necessitating novel treatment strategies.
Purpose of the Study:
- To review recent advances in novel targeted therapies for pancreatic adenocarcinoma.
- To highlight emerging therapeutic strategies targeting key molecular pathways in PDAC.
Main Methods:
- Literature review of recent advancements in targeted therapies for pancreatic cancer.
- Exploration of novel therapeutic strategies targeting KRAS, NRG1, NTRK/ROS1, RET, PRMT5/CDKN2A/MAT2A, EGFR, and Claudin18.2.
Main Results:
- KRAS pathway inhibition strategies include direct therapies, signaling modulation, siRNA, and combination treatments.
- Emerging targets like NRG1, NTRK/ROS1, RET fusions, and PRMT5 axis alterations show therapeutic promise.
- Novel approaches for microsatellite instability-high (MSIH) PDAC and advanced therapies like CAR-T, TCR, TIL, cancer vaccines, and TME modulation are discussed.
Conclusions:
- Rapid advancements in targeted therapies provide renewed optimism for treating pancreatic cancer.
- These novel strategies offer potential for improved outcomes in a historically challenging malignancy.
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