New pharmaceutical compounds that make pancreatic cancer cells more susceptible to chemotherapy
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New pharmaceutical compounds that make pancreatic cancer cells more susceptible to chemotherapy.
Pancreatic cancer is one of the common malignant tumors, and is known as the “King of Cancer” in the field of tumors.
A recent study published in “Science Translational Medicine” found a drug compound that makes pancreatic cancer cells more susceptible to chemotherapy, and it may also reduce some of the devastating side effects of FOLFIRINOX, which is commonly used to treat pancreatic cancer.
The study also found that ATI-450 combined with chemotherapy can help increase the survival rate of pancreatic cancer.
Pancreatic cancer is very difficult to treat. When it is discovered, the cancer is usually in an advanced stage, and the patient usually does not live for a year after diagnosis.
Active chemotherapy is the first-line treatment, but the side effects can be serious, and many tumors will stop responding to treatment.
Now, researchers at Washington University School of Medicine in St. Louis have discovered a drug compound that makes pancreatic cancer cells more susceptible to chemotherapy .
In a study of mice, they found evidence that the drug may also reduce some of the damage of the chemotherapy cocktail FOLFIRINOX (composed of leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) commonly used to treat pancreatic cancer Sexual side effects.
The research titled ” The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress ” was published in the December 1st issue of ” Science Translational Medicine “.
Senior author and medical oncologist Kian-Huat Lim , MD (Associate Professor of Medicine) said: “Pancreatic cancer urgently needs new and better treatments.
The drugs we use now are very effective, but they often cause serious side effects. , So it’s impossible to add more chemotherapy.
This new drug seems to weaken the cancer cells and make them more sensitive to this particular chemotherapy regimen.
In fact, mice receiving chemotherapy plus this drug seem to be better than mice receiving only chemotherapy Healthier, so this new medicine may reduce side effects.
The drug, called ATI-450 , is an anti-inflammatory therapy and is currently undergoing clinical trials for the treatment of rheumatoid arthritis .
FOLFIRINOX is the first-line treatment for pancreatic cancer, but only about one-third of patients have their tumors shrunk after this treatment.
Even so, this reaction can only last for 6 to 7 months . Side effects are common and include nausea, vomiting, diarrhea, fatigue, hair loss, decreased blood cells, and loss of appetite.
As part of their research, the researchers discovered that a molecule called MK2 is critical in allowing pancreatic tumor cells to survive chemotherapy.
This molecule is highly active in pancreatic cancer cells, and it opens signaling pathways that are conducive to survival and reduce cell death. Since ATI-450 is an MK2 inhibitor, it is a very attractive anti-tumor drug.
Dr. Patrick M. Grierson , the first author, medical oncologist and assistant professor of medicine , said: ” MK2 activates a pro-survival mechanism that adapts cancer cells to the severe pressure of chemotherapy.
It can also inhibit a type of cell death called apoptosis, thereby Prevent tumor cells from dying during chemotherapy.
This new drug inhibits MK2, so when mice receive the drug while receiving chemotherapy, tumor cells are more likely to die. “
Lim and Grierson in Barnes – Siteman Cancer Center at the Jewish Hospital and Washington University School of Medicine treatment of pancreatic cancer patients, they tested the drug’s effect on colleagues and cultured in the laboratory pancreatic cancer cell line , containing human pancreatic In mice with cancer cells, as well as in mice that naturally develop pancreatic cancer, because their genes are more susceptible to the disease.
Compared with chemotherapy alone, ATI-450 combined with chemotherapy can reduce tumors by about half .
The mice that received the combination therapy also survived longer, surviving an average of 41 days after starting the treatment , while the mice receiving chemotherapy alone survived an average of 28 days .
“Nearly 50 percent survival rate increase is a significant improvement,” Grierson says, “In addition, impressive is that this drug does not increase the side effects . But for pancreatic cancer chemotherapy have a concern that the merger Other drugs will make the treatment more unbearable . We have monitored blood cell counts and assessed the toxicity of the small intestine and colon. We often see restrictive toxicity and the side effects of the combination therapy have not worsened .”
Lim added: “Many of the side effects of chemotherapy are due to inflammation caused by a molecule called cytokine .A successful benchmark for the treatment of rheumatoid arthritis is the reduction of these cytokines . This drug was originally designed for this disease. Developed. We may have seen the same effect on these mice.”
Researchers plan to continue to study the therapeutic effects of ATI-450 on pancreatic cancer, including whether the drug plus chemotherapy can be combined with other research treatments, such as immunotherapy.
The researchers also said that the drug has the potential to improve the treatment of other cancers that use similar chemotherapy regimens, including colon and other gastrointestinal cancers.
New pharmaceutical compounds that make pancreatic cancer cells more susceptible to chemotherapy
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