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Overcoming drug resistance in pancreatic cancer
Jiang Long1, Yuqing Zhang, Xianjun Yu
1Baylor College of Medicine, Molecular Surgeon Research Center, Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Houston, Texas 77030, USA.
Introduction:
Pancreatic cancer has the worst survival rate of all cancers. The current standard care for metastatic pancreatic cancer is gemcitabine, however, the success of this treatment is poor and overall survival has not improved for decades. Drug resistance (both intrinsic and acquired) is thought to be a major reason for the limited benefit of most pancreatic cancer therapies.
Areas Covered:
Previous studies have indicated various mechanisms of drug resistance in pancreatic cancer, including changes in individual genes or signaling pathways, the influence of the tumor microenvironment, and the presence of highly resistant stem cells. This review summarizes recent advances in the mechanisms of drug resistance in pancreatic cancer and potential strategies to overcome this.
Expert Opinion:
Increasing drug delivery efficiency and decreasing drug resistance is the current aim in pancreatic cancer treatment, and will also benefit the treatment of other cancers. Understanding the molecular and cellular basis of drug resistance in pancreatic cancer will lead to the development of novel therapeutic strategies with the potential to sensitize pancreatic cancer to chemotherapy, and to increase the efficacy of current treatments in a wide variety of human cancers.
Insights
Pancreatic cancer drug resistance limits treatment success. Understanding resistance mechanisms is key to developing new therapies that improve survival for pancreatic cancer and other cancers.
Area of Science:
- Oncology
- Cancer Biology
- Drug Discovery
Background:
- Pancreatic cancer exhibits the lowest survival rates among all cancers.
- Gemcitabine, the standard treatment for metastatic pancreatic cancer, offers limited efficacy due to widespread drug resistance.
- Decades of research have seen minimal improvement in overall survival for pancreatic cancer patients.
Purpose of the Study:
- To review recent advancements in understanding pancreatic cancer drug resistance mechanisms.
- To explore potential strategies for overcoming drug resistance in pancreatic cancer treatment.
Main Methods:
- Review of existing literature on pancreatic cancer drug resistance.
- Analysis of molecular, cellular, and microenvironmental factors contributing to resistance.
- Synthesis of current research on therapeutic strategies to combat resistance.
Main Results:
- Drug resistance in pancreatic cancer arises from genetic alterations, signaling pathway dysregulation, tumor microenvironment interactions, and cancer stem cells.
- Multiple mechanisms contribute to both intrinsic and acquired gemcitabine resistance.
- Recent studies highlight novel approaches to target these resistance pathways.
Conclusions:
- Enhancing drug delivery and overcoming drug resistance are critical goals for pancreatic cancer therapy.
- Understanding the molecular basis of resistance will enable the development of novel therapeutics.
- These advancements hold promise for sensitizing pancreatic cancer to chemotherapy and improving treatment efficacy across various human cancers.
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