Maze representing the complexity of pancreatic cancer

Cracking the Code: How to Stop Pancreatic Cancer's Deadly Spread

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Reese Marlowe in Health & Wellness December 2025 • 4 min read.

"New Research Reveals Potential Targets for Disrupting Pancreatic Cancer Metastasis and Improving Treatment"


Pancreatic cancer is one of the deadliest forms of cancer, notorious for its aggressive spread and limited treatment options. The majority of patients face a grim prognosis, highlighting the urgent need for innovative therapeutic strategies.

Two recent studies presented at a major cancer conference offer promising insights into tackling this disease. One focuses on inhibiting a specific protein that promotes cancer cell survival and proliferation, while the other explores how to disrupt the process by which pancreatic cancer cells spread to other parts of the body.

This article breaks down these findings, explaining how they could lead to more effective treatments and improved outcomes for patients with pancreatic cancer.

Targeting P90-RSK: A Synthetic Lethal Approach

Maze representing the complexity of pancreatic cancer

One study homes in on the protein p90 ribosomal S6 kinase (RSK), particularly the RSK3 variant, as a potential target for therapy. The research team recognized that directly inhibiting RSK3 has proven difficult due to a lack of selective and effective inhibitors. Therefore, they pursued a "synthetic lethal" strategy. This approach exploits the reliance of cancer cells on specific proteins or pathways, meaning that inhibiting RSK3 is only lethal to cancer cells when another key pathway, such as the EGFR pathway, is also blocked.

To identify compounds that could synergize with EGFR inhibitors, the researchers screened approximately 40,000 different molecules. They focused on finding compounds that, when combined with EGFR inhibition, would result in the greatest reduction in cancer cell viability.

  • Compound Screening: Researchers screened 40,000 compounds to identify those that, combined with EGFR inhibition, best reduced cancer cell viability.
  • RSK3 Inhibition: Selected compounds effectively inhibited RSK3, decreasing phosphorylation of downstream targets.
  • Reduced Proliferation: Treatment with the identified inhibitors led to a significant reduction in the proliferation and viability of pancreatic cancer cells.
  • Apoptosis Induction: The inhibitors induced apoptosis (programmed cell death) in cancer cells, showing a synergistic effect when combined with the EGF signaling inhibitor Erlotinib.
The results suggest that pharmacological inhibition of RSK3 reduces proliferation and induces apoptosis (cell death) in pancreatic cancer cell lines. This synthetic lethal approach offers a new avenue for preclinical studies, either alone or alongside other molecularly targeted drugs like EGFR inhibitors.

Disrupting EMT: Halting the Spread of Pancreatic Cancer

The second study investigates the epithelial-to-mesenchymal transition (EMT), a process by which cancer cells transform and gain the ability to invade other tissues and organs. EMT is a critical step in metastasis, the primary driver of cancer-related deaths.

Researchers found that pancreatic ductal adenocarcinoma (PDAC) cells display substantial heterogeneity in their EMT marker expression and ability to undergo EMT. Even cells with the same genetic makeup can exhibit different responses to EMT-inducing signals, suggesting that tumors with similar genetic backgrounds could evolve different routes toward metastasis.

This discovery highlights the complexity of pancreatic cancer and suggests that a more personalized approach is needed to optimize treatment options. By understanding the specific mechanisms driving EMT in individual patients, clinicians may be able to develop more effective strategies to prevent metastasis and improve outcomes.

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: 10.1016/j.pan.2018.05.328, Alternate LINK

Title: P90-Rsk As A Synthetic Lethal Target In Pancreatic Cancer - Molecular Characterization And Therapeutic Inhibition

Subject: Gastroenterology

Journal: Pancreatology

Publisher: Elsevier BV

Authors: Jan Riedel, Nada Milosevic, Jens Von Kries, Marc Nazare, Heidi Griesmann, Patrick Michl

Published: 2018-06-01

Everything You Need To Know

1

What makes pancreatic cancer so dangerous?

Pancreatic cancer is a particularly aggressive form of cancer known for its deadly spread and very limited treatment options. Its aggressiveness leads to a grim prognosis for most patients. The research highlighted focuses on innovative strategies to improve outcomes for those affected by this disease.

2

What is the focus of the research on RSK3 and what approach is being used?

The research targets the protein p90 ribosomal S6 kinase (RSK), specifically the RSK3 variant. Due to the difficulty in directly inhibiting RSK3, a "synthetic lethal" approach is used. This approach means that the cancer cells are highly dependent on specific pathways. The research is screening for compounds that when combined with EGFR inhibitors will significantly reduce cancer cell viability.

3

What is EMT and why is it important in the context of pancreatic cancer?

The process of epithelial-to-mesenchymal transition (EMT) is where cancer cells transform and gain the ability to invade other tissues and organs. This is a crucial step in metastasis, the main cause of cancer-related deaths. Disruption of EMT is therefore a key strategy for halting the spread of pancreatic cancer.

4

How did the researchers identify the compounds that target RSK3?

Researchers screened approximately 40,000 different molecules to find compounds that could synergize with EGFR inhibitors. Their aim was to find the best combination to reduce cancer cell viability. This compound screening led to the identification of inhibitors that effectively target RSK3, decreasing the phosphorylation of its downstream targets. These inhibitors also led to a significant reduction in the proliferation and viability of the cancer cells, and induced apoptosis (programmed cell death).

5

What are the implications of the RSK3 inhibitors identified in this research?

The inhibitors identified in the study demonstrated the ability to reduce the proliferation and induce apoptosis in pancreatic cancer cell lines. This synthetic lethal approach provides a new avenue for preclinical studies. The approach can be used either alone or with other molecularly targeted drugs like EGFR inhibitors. The overall aim of the research is to enhance treatment effectiveness and improve outcomes for pancreatic cancer patients.

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