A maze symbolizing drug resistance in pancreatic cancer, with a path being cleared by PRMT3 inhibition.

Pancreatic Cancer Breakthrough: New Hope in Overcoming Chemoresistance

Lena Kashyap in Health & Wellness December 2025 • 4 min read.

"Scientists identify a novel mechanism by which pancreatic cancer cells develop resistance to chemotherapy, paving the way for innovative treatment strategies."

Pancreatic cancer remains one of the deadliest forms of cancer, characterized by its aggressive nature and poor response to conventional treatments. Despite advancements in cancer therapy, the five-year survival rate for pancreatic cancer is less than 8%. Surgical resection, while potentially curative, is only an option for about 20% of patients due to the cancer's often advanced stage at diagnosis.

For patients with locally advanced or metastatic tumors, chemotherapy is the primary treatment approach. Gemcitabine (GEM) has been a standard first-line treatment since the late 1990s, initially showing promise in controlling tumor growth. However, many patients eventually develop resistance to gemcitabine, rendering the treatment ineffective and contributing to the cancer's grim prognosis.

Recent research has focused on understanding the mechanisms behind chemoresistance in pancreatic cancer. Epigenetic modifications, such as DNA methylation and histone modification, have emerged as significant factors. A groundbreaking study published in 'Cancers' reveals a novel mechanism involving protein arginine methyltransferase 3 (PRMT3), offering new hope for overcoming drug resistance and improving treatment outcomes.

Unlocking the Mystery of Chemoresistance: The Role of PRMT3

A maze symbolizing drug resistance in pancreatic cancer, with a path being cleared by PRMT3 inhibition.

The study, led by researchers at the National Institute of Cancer Research and Kaohsiung Medical University, investigated the role of PRMT3 in gemcitabine resistance. Previous research indicated that PRMT3, an epigenetic modifying enzyme, is dysregulated in gemcitabine-resistant pancreatic cancer cells. This new research aimed to elucidate how PRMT3 contributes to this resistance.

The researchers found that overexpression of PRMT3 led to increased resistance to gemcitabine in pancreatic cancer cells, while reducing PRMT3 restored sensitivity to the drug. This crucial finding highlights PRMT3 as a key player in the chemoresistance process. Further investigation identified ATP-binding cassette subfamily G member 2 (ABCG2) as a novel PRMT3 target. ABCG2 is a well-known contributor to drug resistance in various cancers.

PRMT3 Overexpression:Increases resistance to gemcitabine.
ABCG2 Identification:Identified as a novel PRMT3 target.
mRNA Stability:PRMT3 upregulates ABCG2 expression by increasing its mRNA stability.

The study further revealed that PRMT3 upregulates ABCG2 expression by increasing its mRNA stability. This means that PRMT3 helps ABCG2 mRNA last longer, leading to increased production of the ABCG2 protein. ABCG2 functions as a drug efflux pump, actively removing gemcitabine from cancer cells and reducing its effectiveness. This mechanism directly contributes to the development of chemoresistance.

A Novel Target for Treatment

These findings provide a potential novel strategy for treating gemcitabine-resistant pancreatic cancer. By inhibiting PRMT3, researchers may be able to reduce ABCG2 expression and restore cancer cells' sensitivity to chemotherapy. This approach could significantly improve treatment outcomes for patients with this deadly disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3390/cancers11010008, Alternate LINK

Title: Protein Arginine Methyltransferase 3 Enhances Chemoresistance In Pancreatic Cancer By Methylating Hnrnpa1 To Increase Abcg2 Expression

Subject: Cancer Research

Journal: Cancers

Publisher: MDPI AG

Authors: Ming-Chuan Hsu, Mei-Ren Pan, Pei-Yi Chu, Ya-Li Tsai, Chia-Hua Tsai, Yan-Shen Shan, Li-Tzong Chen, Wen-Chun Hung

Published: 2018-12-20

Everything You Need To Know

What makes pancreatic cancer so difficult to treat?

Pancreatic cancer is a particularly aggressive form of cancer with a very low five-year survival rate. It often goes undetected until it reaches an advanced stage, making effective treatment challenging. Traditional approaches, such as surgical resection, are only viable for a small percentage of patients. For the majority, chemotherapy with Gemcitabine is the primary treatment, but the development of chemoresistance significantly limits its effectiveness.

What is the role of PRMT3 in pancreatic cancer?

PRMT3, or protein arginine methyltransferase 3, is an epigenetic modifying enzyme. Research shows that it plays a significant role in pancreatic cancer's resistance to chemotherapy. The study highlighted in the context reveals that PRMT3 is dysregulated in gemcitabine-resistant pancreatic cancer cells. Overexpression of PRMT3 leads to increased resistance to Gemcitabine. Conversely, reducing PRMT3 restored sensitivity to the drug, highlighting its critical role in chemoresistance.

What is the significance of ABCG2 in the context of pancreatic cancer treatment?

ABCG2 is a protein, specifically a drug efflux pump, identified as a novel target of PRMT3. This protein actively removes Gemcitabine from cancer cells, thereby reducing the drug's effectiveness. The study shows that PRMT3 increases the expression of ABCG2 by increasing its mRNA stability. This means more ABCG2 protein is produced, leading to greater drug efflux and increased chemoresistance. This is a significant finding, as ABCG2 has been associated with drug resistance in various cancers.

How are PRMT3 and ABCG2 related in the process of chemoresistance?

The connection between PRMT3 and ABCG2 lies in how PRMT3 upregulates ABCG2 expression by increasing its mRNA stability. This means PRMT3 helps ABCG2 mRNA last longer, leading to increased production of the ABCG2 protein. ABCG2, acting as a drug efflux pump, actively removes Gemcitabine from the cancer cells, decreasing the drug's effectiveness. This process directly contributes to chemoresistance, a major obstacle in treating pancreatic cancer.

What are the implications of these findings for future treatment strategies?

The study's findings open avenues for novel treatment strategies targeting Gemcitabine-resistant pancreatic cancer. By inhibiting PRMT3, researchers aim to reduce ABCG2 expression, thereby restoring the sensitivity of cancer cells to chemotherapy. This approach could significantly improve treatment outcomes for patients, offering a potential breakthrough in managing this challenging disease. This approach has the potential to improve the treatment outcomes for patients.