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Emerging antibodies for the treatment of pancreatic cancer
Kalliopi Andrikou1, Chiara Peterle1, Stefania Pipitone1
1a Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults , University Hospital of Modena , Modena , Italy.
Introduction:
Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment. This review will underline the most important targeted pathways by mAbs involved in this disease, including EGFR, HER-2, IGF-1 R, VEGF/VEGFR, NOTCH, WNT and immune checkpoints. Expert opinion: Despite the promising results of preclinical and phase I trials, the addition of mAbs to standard chemotherapy or in association with other target agents seems not to confirm these results in the following phase II and III trials in pancreatic cancer patients. However, an improved patient selection before treatment based on molecular characteristics in association with reliable predictive biomarkers can identified more efficacious treatment approaches, minimizing toxicity profile of these drugs.
Insights
Monoclonal antibodies (mAbs) show promise for pancreatic cancer treatment, targeting key pathways like EGFR and VEGF. However, clinical trials indicate limited efficacy, suggesting a need for better patient selection based on molecular markers.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality.
- Understanding tumor molecular biology and microenvironment is crucial for developing targeted therapies.
- Monoclonal antibodies (mAbs) represent a novel targeted treatment strategy for PDAC.
Purpose of the Study:
- To review the efficacy of monoclonal antibodies (mAbs) in pancreatic cancer treatment.
- To identify key targeted pathways (e.g., EGFR, HER-2, VEGF) for mAb therapy in PDAC.
- To evaluate the clinical trial outcomes of mAbs in PDAC patients.
Main Methods:
- Review of preclinical and clinical trial data evaluating mAbs in pancreatic cancer.
- Analysis of targeted pathways including EGFR, HER-2, IGF-1R, VEGF/VEGFR, NOTCH, WNT, and immune checkpoints.
- Evaluation of mAb efficacy in combination with standard chemotherapy or other targeted agents.
Main Results:
- Preclinical and Phase I trials showed promising results for mAbs in PDAC.
- Phase II and III trials did not consistently confirm these positive outcomes when mAbs were added to standard chemotherapy.
- Targeted pathways evaluated include EGFR, HER-2, VEGF, and immune checkpoints.
Conclusions:
- While mAbs offer a potential targeted approach for PDAC, their efficacy in later clinical trials has been limited.
- Improved patient selection using molecular characteristics and predictive biomarkers is essential for optimizing mAb treatment efficacy.
- Personalized treatment strategies are needed to maximize therapeutic benefits and minimize toxicity in pancreatic cancer patients.
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