Nature: a new member of the anticancer drug family

Metformin is a famous hypoglycemic drug, which is mainly used to treat type 2 diabetes, but it also has potential therapeutic effect on many human diseases such as nonalcoholic fatty liver disease and cancer Lovastatin, simvastatin and fluvastatin are all statins, but they are related to the low mortality of 13 kinds of cancer Anti cancer drugs are supposed to be anti-cancer drugs, but some of these "rat and dog" drugs should be replaced by others Recently, an international team of scientists from Denmark, the United States and the Czech Republic found that long-term use of the drug disulfiram reduced the death rate of cancer patients by 34% Breast cancer cells are the target of "drugs for alcoholism" (source: Science) In the 1960s, a cancer doctor published a case A 38 year old breast cancer patient with bone metastases suffered from excessive sadness due to the spread of cancer, leading to severe alcohol abuse For patients, the spread of cancer cells often means a fatal turning point After that, she began to indulge in alcohol, and doctors stopped all cancer treatments The only drug she was given was disulfiram, a drug used to control her drinking behavior Unexpectedly, the patient lived nearly 10 years without any cancer treatment, and finally did not die of cancer, but because of drunk falling from the window To the doctor's surprise, the autopsy found that the tumor transferred to the bone almost disappeared Can drinking cure cancer? It doesn't seem to be, so is it because of the effect of disulfiram In 1993, a small clinical trial of 64 patients with non metastatic high-risk breast cancer showed that compared with chemotherapy alone, the combined chemotherapy of diltiazem could reduce the recurrence rate of breast cancer in 5 years and the mortality rate by nearly 30% In 2015, another clinical trial of 42 patients with stage IV non-small cell lung cancer showed that the combined chemotherapy of dithiolen could prolong the survival of patients by 41% compared with chemotherapy alone Two patients in the control group died within two years Npl4 protein aggregation blocks the formation of p97-npl4 complex (source: nature) Last week, a paper published in nature brought back disulfiram Scientists in Denmark, the United States and the Czech Republic analyzed the data of 240000 cancer patients taking drugs in Denmark, and found that more than 3000 cancer patients who took disulfiram after diagnosis continued to take disulfiram, compared with those who stopped taking 1177 patients, the mortality rate decreased by 34% The antitumor activity of dithiolen was proved in many cancer models, and the molecular mechanism of alcohol abstinence and sulfur inhibition was determined for the first time It was found that the decomposition product of abstinence sulfur in vivo was sodium dithiocarbamate, which formed complex cuet with copper ion The complex cuet can target npl4 and induce aggregation, which can block the formation of p97-npl4 complex, and p97-npl4 usually supports tumor growth, so it has the effect of anti-tumor growth Moreover, disulfiram can selectively enter tumor tissue to avoid injuring normal tissue Disulfiram has been used in clinic for many years, and its safety is reliable But large pharmaceutical companies may not be interested in studying disulfiram because there is no patent protection for the old drug There are many other drugs that can play a role but can not bring commercial value For example, warfarin has recently been found to prevent cancer, aspirin and metformin also have the role of preventing and treating cancer These classic clinical drugs may be ideal drugs for cancer treatment Extended reading of disulfiram, also known as abstinence sulfur, is widely used in patients with alcohol dependence Even if a small amount of alcohol is used after taking the drug, the body will have serious discomfort The discomfort caused by disulfiram is very uncomfortable, and even there is a special clinical symptom called disulfiram reaction, which refers to that disulfiram inhibits aldehyde dehydrogenase, hinders the normal metabolism of ethanol, resulting in the reaction of acetaldehyde poisoning caused by drinking a small amount of ethanol It is not only disulfiram, some clinical drugs have the same molecular structure as disulfiram, and they can also have disulfiram reaction when drinking alcohol Some cephalosporins are common antibiotics, including cefoperazone, ceftriaxone, cefotaxime, etc in addition, some drugs such as metronidazole, ketoconazole, ornidazole, etc can also cause nidazole Thesis link: https://