In this pancreatic tumor, T cells (pink) have infiltrated the tumor cells (green)
Pancreatic cancer is the third most deadly cancer in the United States.
For a long time, researchers have been looking for ways to slow or stop the growth and spread of pancreatic cancer, but chemotherapy and immunotherapy have limited effects
There is new hope for combination medicine
There is new hope for combination medicine Pancreatic ductal adenocarcinoma is highly resistant to current treatments due to its tumor heterogeneity, high degree of connective tissue forming and immunosuppressive tumor microenvironment
In fact, the body’s immune system contains T cells, which can recognize and destroy cells expressing cancer proteins, but most tumors create a highly immunosuppressive environment that disables these T cells and helps tumors survive
The working principle of immune checkpoint therapy is to remove these "brakes" and rejuvenate T cells
Some researchers hypothesized that the reason for the failure may be that pancreatic tumors do not express so many oncoproteins, or neoantigens
Professors such as Lu Kunping and Zhou Xiaozhen of Harvard Medical School in the United States focused on the proline isomerase Pin1
Researchers found that Pin1 is overexpressed in cancer cells and cancer-related fibroblasts of patients with pancreatic ductal adenocarcinoma, and that high Pin1 expression is associated with poor survival of patients
The researchers said that in a mouse model of pancreatic cancer that introduced two oncogenes Kras and p53 mutations, if only gemcitabine and PD-1 inhibitors were used, most of the mice died within 3 months
The reason may be that targeting Pin1 can block multiple cancer signaling pathways at the same time, and by acting on cancer-related fibroblasts, it can relieve the immunosuppressive nature of the tumor microenvironment
Another combination drug regimen aimed at pancreatic cancer drug resistance has also achieved good results
"China Science News" learned from the Massachusetts Institute of Technology that in the study of mouse pancreatic cancer models, researchers at the institution found that most pancreatic cancer cells express a protein called CD155, which activates a T-cell called TIGIT Receptor
The researchers tested a variety of drug combinations that inhibit PD-1, TIGIT experimental drugs, and CD40 agonist antibodies
However, when they combined CD40 agonist antibodies, PD-1 inhibitors, and TIGIT inhibitors, about half of pancreatic cancers shrank, and in 25% of mice, the tumors disappeared completely
"Pancreatic cancer is a devastating disease clinically
.
" said William Freed-Pastor of the Koch Institute for Comprehensive Cancer Research and the corresponding author of the paper.
"If this method can produce a lasting response in patients , It will have a major impact on the lives of at least some patients
.
"
Start with iron in another way
Start with iron in another way Part of the success of pancreatic cancer lies in its ability to cleverly reconnect normal cell survival mechanisms to maintain its own nutritional supply and maintain expansion
.
A new study led by a research team at the University of Michigan Rogge Cancer Center shows how inhibiting a key enzyme called GOT1 can turn on a switch in such cancer cells-making them move from using nutrients to promote growth to preserving nutrients Matter to maintain energy levels
.
On August 11, the results of a cell culture study published in Nature Communications showed that in this state, cancer cells release iron reserves and are susceptible to a programmed, iron-dependent form of cell death -The impact of iron death
.
Iron death is an iron-dependent, new type of programmed cell death that is different from apoptosis, cell necrosis, and autophagy
.
One of the main mechanisms of iron death is that under the action of divalent iron or ester oxygenase, it catalyzes the occurrence of lipid peroxidation of unsaturated fatty acids highly expressed on the cell membrane, thereby inducing cell death
.
"If the'hegemony' of pancreatic cancer comes from a different way of nutritional metabolism from other cancers, our goal is to target all aspects of metabolism in order to obtain therapeutic benefits
.
" said Costas Lyssiotis, the corresponding author of the paper
.
The GOT1 pathway can help cancer cells maintain energy balance
.
Researchers found that GOT1 can inhibit mitochondrial metabolism and promote catabolism.
After knocking down the level of GOT1, cells are prone to iron death
.
The researchers said that this mainly enhances the availability of unstable iron through autophagy
.
"When we inhibit this enzyme, it will not kill the cell, but it will put the cell in a state of tension, so it must use these nutrients to maintain the status quo, not growth
.
" Lyssiotis said
.
Research diversity has not changed for more than a decade
Research diversity has not changed for more than a decade Although there are frequent good news, the problems in clinical research of pancreatic cancer in the United States cannot be underestimated
.
On August 17, researchers stated in Gastroenterology that when analyzing the latest advances in the treatment of pancreatic cancer, they found that black Americans, Hispanics, and Native Americans were still absent from relevant clinical trials
.
The researchers searched the database of pancreatic cancer treatment clinical trials conducted in the United States from 2005 to 2020, and focused on the results of trials-a total of 207 trials with a total of 8,429 participants
.
The data shows that in the past 15 years, pancreatic cancer trials have reported a steady increase in the proportion of participants by ethnicity
.
However, the actual participation rate of minority participants has not changed and has remained at a disproportionately low level for more than a decade
.
The lead author of the paper, Kelly Herremans, a surgical resident at the University of Florida School of Medicine, said: "The current regulations only require the number of reports, but there are no requirements for who is actually included in the clinical trial
.
The reality is shocking to me
.
"
Specifically, of all pancreatic cancer clinical trial participants, only 8% were black, Hispanics accounted for 6% of trial participants, and Aboriginals accounted for 0.
3%
.
"If clinical trials do not have good diversity, how do we know if certain drugs are more effective in certain populations?" said Jose Trevino, the corresponding author of the paper and chief surgeon at the University of Virginia Massey Cancer Center.
Very good treatment options for ethnic and minority patients
.
"
Related paper information: https://doi.
org/10.
1016/j.
cell.
2021.
07.
020
https://doi.
org/10.
1016/j.
cell.
2021.
07.
020 https://doi.
org/10.
1016/j.
ccell.
2021.
07.
007
https://doi.
org/10.
1038/s41467-021-24859-2
https://doi.
org/10.
1053/j.
gastro.
2021.
06.
079
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