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Researchers at Princeton University have discovered a compound that targets the central metastasis gene of many common cancers.
According to the New Atlas, the mysterious ways in which cancer spreads in the body in a process known as “metastasis” is what can turn cancer into a major enemy that makes it difficult to fight.
Researchers at Princeton University have been working on this for more than 15 years, focusing on a central gene in the ability of most common cancers to metastasize. They have now discovered what they describe as a “silver bullet” in the form of a compound that could deactivate the gene in mice and human tissue, and possibly clinical trials soon to have a direct effect on humans. Review.
Metastatic cancer is a key area of focus for researchers because it is actually the leading cause of death from the disease. While surgery or chemotherapy may be effective in killing the primary tumor, the cells that are affected by the tumor and remain in the body can carefully and silently make their way around the body and months or even years later. Create new tumors.
Metastasis is the spread of cancer cells from one tissue to another. These types of tumors are also called metastatic tumors. In some tumor cells, the characteristics of the primary cell change slightly, and the tumor cell is still more or less similar to the original cell from which it originated.
“Metastatic breast cancer causes more than 40,000 deaths annually in the United States, and patients do not respond to standard treatments such as chemotherapy, targeted therapies and immunotherapy,” said Minhong Shen, a member of the Princeton team.
“Our study identified a set of chemical compounds that can significantly increase the response rate to chemotherapy and immunotherapy in models of mice with metastatic breast cancer.” These compounds have high therapeutic potential.
The discovery is rooted in a 2004 study in which Princeton scientists identified a gene called methadone (MTDH) that is involved in metastatic breast cancer.
A 2009 article published by cancer biologist Yabin Kang found that the gene amplifies about one-third of breast cancer tumors and produces abnormally high levels of MTDH proteins, not only in the process of metastasis, but also in The resistance of those tumors to chemotherapy also plays an important role.
“There was a lot of excitement at the time and we were saying, ‘Wow, we found a metastasis gene that is associated with poor treatment outcomes in patients,'” Kang said. What next? Can we target it?
This was a big question, because at that time no one knew how this obscure and lesser-known gene worked, because it bore no resemblance to any other known human protein.
Subsequent research continued to shed light on the importance of the MTDH gene and showed how it is vital for cancer growth and metastasis. Genetically engineered mice lacking the gene grew naturally, and those with breast cancer had far fewer tumors, and those tumors that formed did not metastasize.
It was later found that the same was true of prostate cancer, lung cancer, colon cancer, liver cancer and many other cancers.
“So we found that the presence of this gene is essentially essential for the progression of cancer and all the horrible things about cancer,” he said. Mice can grow, reproduce and live normally without this gene, so we know this would be a great drug target.
The crystalline structure of MTDH indicates that the protein has a pair of finger-like protrusions that are joined by two holes in the surface of another protein called SND1. According to Kang, this is like dipping two fingers into the holes of a bowling ball, and the scientists wanted to see if this intimate connection could be broken, if it could reduce the harmful effects of MTDH.
“We knew what the shape of the keyhole was from the crystal structure, so we kept searching to find the key,” says Kang.
The team spent two years searching and screening to find the right molecules to fill the holes, and until recently they did not have much success until they came up with what they called “silver bullets” that could fill the holes. Block and prevent proteins from sticking together.
“In 2014, we showed what happens if you kill a gene at birth,” says Kang. This time we show that we can block the function of this gene after the tumor has become completely cancerous and life-threatening. We found that the same result can be achieved with either genetic therapy or medication.
Scientists say that MTDH helps cancer in two main ways; By helping tumors to withstand the pressures of chemotherapy and by turning off the alarms that normally sound when organs are attacked. This gene, entangled with the “SND1” protein, prevents the immune system from detecting dangerous signals normally produced by cancer cells and thus preventing the immune system from attacking them.
Locked up.
“Now with this combination, we’re reactivating the alarm system,” says Kang.
The team is currently working to refine the compound and hopes to improve its effectiveness in breaking the link between the MTDH gene and the SND1 protein and reduce its required dose.
Researchers hope the compound will be ready for clinical trials in human patients in the next two to three years.
“In the two articles we published, we identify a compound and show that it is effective against cancer, and we show that it is very, very effective when combined with chemotherapy and immunotherapy,” says Kang. Although metastatic cancers are frightening, by understanding how they work and their dependence on specific key pathways such as MTDH, we can attack and treat them prone to nclhk.
The study is published in two articles in the journal Nature Cancer.