August 17, 2022

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Can pancreatic cancer be reversed into a cyst?

Can pancreatic cancer be reversed into a cyst?



 

Can pancreatic cancer be reversed into a cyst?

“Nature” heavyweight: reversing the “cancer king” into a cyst? ! Scientists may have found the key to scientific discovery.

It is already 2022, and pancreatic cancer is still a well-deserved “cancer king”.

 

At the beginning of this year, the latest data released by the American Cancer Society showed that the 5-year survival rate of pancreatic cancer patients in the United States is 11% [1]. In other words, only one in ten pancreatic cancer patients in the United States survives 5 years or more.

 

The reason why pancreatic cancer is so brutal is that a large part of the reason is that the onset is hidden, and most patients are found at an advanced stage.

 

Just last month, a study led by a team at the Johns Hopkins Pancreatic Cancer Center found that the majority of pancreatic cancers diagnosed through screening were diagnosed at stage I, and these patients had a better five-year survival rate.

Reached 73.3%, and the median overall survival was nearly 10 years ; while the majority of pancreatic cancer patients diagnosed outside screening were advanced, and the median overall survival was only 1.5 years !

 

Therefore, in order to remove the “crown” of pancreatic cancer, the key lies in early detection and early treatment. However, early detection is really not easy, otherwise the 5-year survival rate by 2022 is only 11% [1].

 

So can we change our thinking: If early detection is too difficult, can we “turn back the clock” and bring advanced pancreatic cancer back to the early stage? ! !

 

This is indeed a bold idea.

 

Unexpectedly, a research team led by Axel Behrens of the Institute of Cancer Research in London, England, may have really found a way to “turn back the clock” .

 

Recently, a team led by Behrens published important research results in the top journal “Nature” [3]. They found that a protein called GREM1 is very important for pancreatic cancer. If GREM1 is inactivated, pancreatic epithelial cells can become pancreatic cancer cells within a few days; and if GREM1 is overexpressed in cancer cells, almost all of the cancer cells are “epithelialized”!

 

What do you mean? ! !

 

Simply put, if there is a high amount of GREM1 protein in pancreatic cancer cells, this causes the pancreatic cancer cells to revert to an almost epithelial state . To put it more bluntly, pancreatic cancer may become a low-grade cyst !

 

It is worth mentioning that Professor He Yulong, Professor Zhang Changhua and Huafu Li from the Center for Digestive Medicine of the Seventh Affiliated Hospital of Sun Yat-Sen University also made important contributions to this research .

 

 

Can pancreatic cancer be reversed into a cyst?

 

Next, let’s take a look at how scientists discovered the function of GREM1.

 

Based on studies on mouse models of pancreatic ductal adenocarcinomas (PDACs, which account for about 90% of all pancreatic cancers[4]) and analysis of the Human Cancer Genome Atlas (TCGA) database, Behrens’ team found that GREM1 is associated with the occurrence of pancreatic ductal adenocarcinomas Development exists.

 

To understand the effect of GREM1 on pancreatic ductal adenocarcinoma progression, the researchers first knocked out the Grem1 gene in specific pancreatic ductal adenocarcinoma model mice.

The results of the study were surprising: 90% of the mice in which the Grem1 gene was knocked out developed pancreatic cancer liver metastases, while only 15% of the mice in which the Grem1 gene was still present developed pancreatic cancer liver metastases . If you compare liver metastases, there are more model mice with Grem1 knockout.

 

 

From histological point of view, the liver metastases of Grem1 knockout mice were less differentiated (high malignancy) , while the liver metastases of Grem1 normal mice were highly differentiated (low malignancy) .

 

Subsequently, Behrens’ team analyzed data from a large cohort of primary and metastatic human pancreatic ductal adenocarcinomas and found that Grem1 gene expression was significantly reduced in metastases .

 

These data suggest that inactivation of the Grem1 gene leads to increased malignancy and metastases in pancreatic ductal adenocarcinoma.

 

Can pancreatic cancer be reversed into a cyst?

Effect of Grem1 gene deletion on the development of pancreatic ductal adenocarcinoma

 

Then it’s time to witness the miracle.

 

To further verify the function of the GREM1 protein, Behrens’ team overexpressed the Grem1 gene in specific genotypes of pancreatic ductal adenocarcinoma organoids, then transplanted these organoids into mice, and found that those organoids became well -differentiated Cystic tumor , the number of malignant tumor cells is significantly reduced .

 

Overexpressing the Grem1 gene in a human pancreatic ductal adenocarcinoma cell line , Behrens and colleagues also observed increased levels of epithelial markers, suggesting that this mechanism may also exist in humans.

 

Can pancreatic cancer be reversed into a cyst?

Effects of Grem1 gene overexpression on the development of pancreatic ductal adenocarcinoma

 

As for the specific molecular mechanism behind it, the Behrens team also conducted in-depth research, and finally found that GREM1 protein affects the progression of pancreatic ductal adenocarcinoma by regulating bone morphogenetic proteins (BMPs), which in turn can regulate the level of GREM1 protein, form a self-inhibitory feedback loop .

 

Can pancreatic cancer be reversed into a cyst?

Schematic diagram of the mechanism

 

Based on the above research results, it is not difficult to find that the Behrens team’s research progress is very important, which has opened up a new way for the treatment of pancreatic cancer, and is expected to remove the “crown” on the head of pancreatic cancer.

 

Behrens agrees that the work they have done in the lab shows that it is possible to reverse the cell fate of pancreatic cancer, “reversing” time in this aggressive tumor and returning it to a more treatable one status .

 

 

 

 

 

 

references:

[1]. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33. doi:10.3322/caac.21708

[2]. Dbouk M, Katona BW, Brand RE, et al. The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival. J Clin Oncol. 2022; JCO2200298. doi:10.1200/JCO.22.00298

[3]. Lan L, Evan T, Li H, et al. GREM1 is required to maintain cellular heterogeneity in pancreatic cancer. Nature. 2022;607(7917):163-168. doi:10.1038/s41586-022-04888- 7

[4]. Park W, Chawla A, O’Reilly EM. Pancreatic Cancer: A Review. JAMA. 2021;326(9):851-862. doi:10.1001/jama.2021.13027

[5]. https://www.icr.ac.uk/news-archive/scientists-discover-mechanism-controlling-spread-of-pancreatic-cancer

Can pancreatic cancer be reversed into a cyst?

(source:internet, reference only)


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