Hepatology: a leukemia therapy currently in use or expected to treat intrahepatic cholangiocarcinoma
2021-06-21
June 12, 2021 / Bio Valley BIOON/ - cholangiocarcinoma is a rare and aggressive cancer that affects more than 2000 patients in the UK every year. However, the incidence rate of cholangiocarcinoma is increasing steadily every year. Researchers have speculated that cholangiocarcinoma in the future will be as common as breast cancer. Intrahepatic cholangiocarcinoma (ICC) is a highly invasive liver cancer. At present, patients are in urgent need of treatment. Abnormal activation of c-jun-N-terminal kinase (JNK) pathway is the key feature of ICC, and it is also an attractive target to develop corresponding targeted therapy. However, it is not clear that JNK activation promotes ICC growth, and how downstream effectors of JNK pathway are used as key targets. It is important that the treatment options of patients are very limited, and the only feasible way to cure cholangiocarcinoma is to remove the tumor by surgery.
Recently, in a research report published in Hepatology, an international magazine entitled "Photoshop translation and stabilization of Pin1 by JNK promote into radiation cholangiocarcinoma growth", scientists from St. James college and other institutions have revealed the key role of JNK signal in the process of ICC, The results of the study may help to develop new treatment methods of ICC. Over the past 10 years, researchers have focused on how to target specific genes and proteins in the growth and survival of cancer cells, aiming to better understand the types of tumors; In the process, researchers have witnessed the development of a large number of new drugs, some of which can help improve the prognosis of specific patients, but there is no cure for cholangiocarcinoma.
In this study, researchers proposed that a special drug called all trans retinoic acid (ATRA) can help treat cholangiocarcinoma. ATRA is an active metabolite of vitamin A, which can participate in cell differentiation and cell death; It is usually used to treat specific types of blood cancer, such as acute promyelocytic leukemia, etc; Although ATRA can treat this type of leukemia, many patients will develop drug resistance, and their research on solid tumor treatment is very limited.
After using mouse model, researchers found that ATRA can reduce tumor size by 40% compared with the control group. ATRA can reduce the incidence of tumor by a specific molecule, such as nuclear retinoic acid receptors, which is a kind of receptor that can control the survival or deletion of specific protein; Recently, studies have shown that ATRA can inhibit the expression and activation of a protein called Pin1, which is a major regulator of oncogene and tumor suppressor in tumor cells.
The results showed that Pin1 was high in liver biopsy tissue of cholangiocarcinoma patients, and ATRA could help to reduce the abundance of Pin1 in the human model of cholangiocarcinoma and cells. The best news is that ATRA may not have a negative effect on healthy cells near the bile duct, which may show the role of Pin1 in inducing tumor and the special antitumor effect of ATRA; In addition, the researchers found that a special protein called JNK may be responsible for promoting the stability of Pin1 and accumulation in cancer cells, which ultimately promotes the progress of the tumor.
Researchers are now studying whether ATRA or other similar therapies are used to inhibit Pin1 to work together with current cholangiocarcinoma therapies (such as cisplatin or gemcitabine), and of course, researchers need to conduct clinical trials in human bodies. But because ATRA is safe and well tolerated, researchers are conducting clinical trials in patients with breast cancer and pancreatic cancer. They hope that the results of this study can quickly enter the clinical trials of cholangiocarcinoma.
In conclusion, the results show that JNK Pin1 regulating axis can be used as an important functional determinant of ICC growth, and can provide a reasonable therapeutic target for JNK activation by inhibiting Pin1.
