Pancreatic Cancer Treatment: The Role of a Brain-Building Protein

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In a groundbreaking study spanning eight years, scientists from Cold Spring Harbor Laboratory (CSHL) and the University of California, Davis, have unveiled a significant breakthrough in pancreatic cancer research.

This discovery sheds light on how pancreatic cancer, one of the deadliest forms of cancer due to its rapid metastasis, exploits a brain-building protein to accelerate its spread.

The findings of this research could pave the way for developing strategies to slow down the disease’s progression, offering new hope in the battle against this aggressive cancer.

Highlights:

Collaborative Breakthrough: Led by Chang-il Hwang, now an assistant professor at UC Davis, alongside CSHL Professors David Tuveson and Christopher Vakoc, the research team has built upon their initial discovery in 2017 about a protein pivotal for initiating metastasis in pancreatic ductal adenocarcinoma (PDAC).
The Culprit Protein – Engrailed-1 (EN-1): EN-1, a transcription factor crucial for brain development, is hijacked by late-stage PDAC to escape the body’s cancer defenses, leading to a more metastatic and fatal progression of the disease.
Function of EN-1: As a transcription factor, EN-1 regulates gene expression timing and duration. Its aberrant expression in pancreatic cancer blocks genes that promote natural cell death, facilitating cancer’s spread.
Organoid-Based Research: Using organoids, or mini-tumors, the researchers identified that suppressing EN-1 expression could allow targeted genes to promote healthy cell survival, potentially slowing cancer progression.
Future Directions: Despite the current challenges in targeting transcription factors with drugs, this research opens up possibilities for disrupting harmful interactions caused by mutated EN-1 in PDAC. Hwang and his team are optimistic about developing personalized therapeutics and treatment strategies by targeting PDAC types dependent on EN-1.

Conclusion:

This pioneering research not only deepens our understanding of pancreatic cancer’s mechanisms but also highlights the innovative use of organoids in cancer research. By pinpointing the role of the EN-1 protein in facilitating the disease’s spread, scientists are now closer to developing targeted treatments that could inhibit this deadly progression.

As pancreatic cancer remains a leading cause of cancer-related deaths, the collaborative efforts of researchers at CSHL and UC Davis mark a significant step towards more effective and personalized treatment options. The journey toward combating aggressive PDAC continues, fueled by the promise of new insights and therapeutic strategies emerging from this vital research.

Journal Reference:

Jihao Xu, Jae‐Seok Roe, EunJung Lee, Claudia Tonelli, Keely Y. Ji, Omar W. Younis, Tim D.D. Somervile, Melissa Yao, Joseph P. Milazzo, Herve Tiriac, Anna M. Kolarzyk, Esak Lee, Jean L. Grem, Audrey J. Lazenby, James A. Grunkemeyer, Michael A. Hollingsworth, Paul M. Grandgenett, Alexander D. Borowsky, Youngkyu Park, Christopher R. Vakoc, David A. Tuveson, Chang‐Il Hwang. Engrailed‐1 Promotes Pancreatic Cancer Metastasis. Advanced Science, 2023; 11 (6) DOI: 10.1002/advs.202308537