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Lab Study Finds Pancreatic Cancer Growth Is Slowed by Blocking the Hhat Enzyme

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Key Points

  • The overexpression of Hedgehog family proteins contributes to the development of many cancers. Blocking the function of the Hedgehog acyltransferase enzyme slows the growth and spread of pancreatic cancer.
  • The Hedgehog pathway is a major regulator of many fundamental processes in vertebrate embryonic development, including stem cell maintenance cell differentiation, tissue polarity, and cell proliferation.
  • Targeting inhibition of the Hedgehog signaling pathway may be effective in the treatment and prevention of many cancers. 

The overexpression of Hedgehog family proteins contributes to the development of many cancers. Research by Konitsiotis et al has found that blocking the function of the Hedgehog acyltransferase (Hhat) enzyme slows the growth and spread of pancreatic cancer. Targeting inhibition of the Hedgehog signaling pathway may be effective in the treatment and prevention of many cancers. The study is published in PLOS ONE.

The Hedgehog pathway is a major regulator of many fundamental processes in vertebrate embryonic development, including stem cell maintenance cell differentiation, tissue polarity, and cell proliferation. While Hedgehog usually switches off when the embryo is formed, in many cancers, including pancreatic, prostate, breast, gastrointestinal, and lung cancers, it becomes abnormally activated.

Promising Pathway

Using genetic techniques, the researchers blocked the Hhat function in pancreatic ductal adenocarcinoma cell lines, and found that the growth and spread of the cancer cells slowed substantially in a test-tube assay. Because the techniques used in the study cannot be duplicated in animal or human studies, the researchers are investigating chemical compounds that could be developed into a new drug to replicate the laboratory effect.

Two of the researchers, Anthony I. Magee, PhD, and Edward W. Tate, PhD, both of the Imperial College London, are reportedly planning to screen a large library of molecules to select the ones whose properties are most likely to inhibit Hhat’s function and then test them in mice.

“Signaling pathways are complex,” Dr. Magee said in a statement. “They’re like a flow diagram, with a multitude of arrows traveling along and splitting off at many points along the way, each initiating a new chain reaction of activity. Whilst you could potentially stop the Hedgehog signal at many points along its journey, we wanted to see if we could simply prevent the process from starting in the first place. This meant stopping Hhat from attaching the fatty molecule to Hedgehog, which is needed for the signaling.”

Targeting inhibition of the Hedgehog signaling pathway may be effective in the treatment and prevention of many cancers, and clinical trials for Hedgehog pathway inhibitors in the treatment of several cancers, including metastatic adenocarcinoma of the pancreas, are underway.

Dr. Magee is the corresponding author for the PLOS ONE article.

This study was supported by grants from the UK Medical Research Council and the Pancreatic Cancer Research Fund. The researchers reported no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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