Acyclic vitamin A Prevents HCC Recurrence

Researchers have found acyclic vitamin A can prevent the recurrence of hepatocellular carcinoma (HCC).

Acyclic retinoids, an artificial compound derived from vitamin A, have been found to prevent the recurrence of the most common liver cancer, hepatocellular carcinoma (HCC). Now, in a study published in the Proceedings of the National Academy of Sciences, scientists have discovered that the compound targets a class of cancer stem cells that prevent them from producing new tumors.

HCC is a highly deadly cancer that causes about 600,000 deaths worldwide each year, making it the second most fatal cancer after NSCLC. One of the reasons for high mortality is its high recurrence rate – surgery and other treatments are initially effective, but cancer often recurs. Therefore, the researchers looked for ways to prevent relapse, and recently found that acyclic vitamin A drugs can effectively prevent the recurrence of tumors. However, scientists are not sure why it works.

In search of clues, a team led by Soichi Kojima of the RIKEN Comprehensive Medical Center studied the transcriptome of cells exposed to an acyclic retinoid and found that they had a low MYCN expression compared to untreated control cells. It is usually expressed in tumors and associated with poor prognosis. Further experiments involving deliberate suppression of gene expression in cancer cells show that a decrease in MYCN expression leads to slower cell cycle progression, proliferation and colony formation, and results in greater cell death, implying an acyclic type on MYCN Visual pigment slows the development of cancer.

The team then focused on the role of “cancer stem cells” – these special cells survived the impact of chemotherapy or other treatments and then differentiated into new cancer cells, which led to recurrence. They found that high expression of MYCN is associated with the expression of many markers associated with cancer stem cells.

“The most interesting part of our discovery,” Kojima said, “is that when we looked at different subpopulations of heterogeneous cancer cells, we discovered a group of specific EpCAM-positive cancer stem cells, with elevated MYCN. The key to the retinol effect lies in its ability to target these liver cancer stem cells. “

In fact, experiments revealed that EpCAM-positive cells were selectively depleted in a dose-dependent manner when exposed to acyclic retinoids. To test whether this is clinically significant, they performed a liver biopsy on patients who had been treated with acyclic retinoids after liver cancer surgery and found that the expression level of MYCN was decreased at high doses of 600 mg/d but not 300 mg/d. , suggesting that MYCN expression in an acyclic retinoid response may be an important part of the observed recurrence differences in the trial.

Finally, they looked at the data in the Cancer Genome Profile and found that elevated MYCN expression was associated with significantly worse prognosis.

According to Kojima, “Amazingly, acyclic retinoids are specifically targeted against certain types of cancer stem cells, which provides us with important tips to reduce cancer recurrence and truly cure patients. We are waiting for clinical data outcome.

Currently, South Korea, Taiwan and Singapore are conducting Phase 3 clinical trials of non-cyclic retinoids (also known as Peretinoin) to test the drug’s ability to prevent recurrence of HCC.

* The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.