Induce "combined fists" to let cancer cells reveal "breaks"

first induces cancer cells to age, and then gives them a lethal precision blow. The new research team of Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine, in collaboration with Rene Bernaz Labs, a professor at the Netherlands Cancer Institute, used gene knock-out screening technique CRISPR-Cas9 in combination with high-volume compound screening to find for the first time the treatment strategy of liver cancer that can be specifically removed by inducing TP53 mutations in liver cancer cells. The findings were published online October 3 in Nature.
cancer is a malignant tumor with multi-gene participation, multi-factor mediatation and complex pathological mechanism. It has been found that the related gene mutations in many signaling paths are closely related to the development of liver cancer, but the main gene mutation types of liver cancer are not directly targeted as effective drugs. Clinically, the use of non-specific multi-target drugs is the standard treatment for patients with advanced liver cancer, but the clinical efficacy is very limited. Anti-cancer chemotherapy drugs developed for the characteristics of cell proliferation kill cancer cells at the same time, but also kill normal cells in the body, can be described as "killing a thousand enemies, self-damaged eight hundred", toxic side effects are serious.
In this study, researchers found for the first time that cell division cycle kinase (CDC7) inhibitors specifically induced the aging of TP53 gene mutation liver cancer cells, while TP53 wild liver cancer cells and normal cells did not have aging induction, and similar experimental results were observed in lung and colon cancer cells. It is reported that TP53 mutation patients accounted for about 35% to 40% of liver cancer patients. At the same time, they found that the depression treatment drug "Sherwood" specifically promotes the apoptosis of these aging liver cancer cells.
the paper's co-author, Yan Wenxin, described the strategy as a "combined fist" treatment model. The first trick is similar to boxing's "fake trick", that is, the use of tumor cells exist in the specific mutation, it is specifically induced to a specific state, such as cell aging state, so that tumor cells show "cracks", and other proliferation of normal cells in the human body has no effect or less impact. The second trick is "real-world", which is to specifically remove aging tumor cells.
, the team has now confirmed in animal models of liver cancer that the combined use of CDC7 inhibitors and mTOR inhibitors can significantly inhibit the progression of liver cancer, which is superior to the multi-target drug soraphinib and so on. "Cdc7 inhibitors and mTOR inhibitors are currently in clinical trials and are expected to provide new approaches to liver cancer treatment." If clinical trials are positive, the drugs will be mainly used in the diagnosis and treatment of patients with advanced liver cancer in the future, He said. (Source: Huang Xin Yuan, China Science Journal
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