New Cure for Cancer Discovered, Save Lots of Lives

Recently, Nature, the world’s top journal, has thrown a super heavyweight bomb:

Researchers from Denmark, the United States and the Czech Republic collaborated to analyze the medical data of 240,000 cancer patients in Denmark and found that mortality of patients with long-term use of disulfiram decreased by 34%, compared with those who did not use disulfiram.

Also, they identified the specific mechanism by which disulfiram inhibits cancer and demonstrated its anticancer activity in a variety of cancer models for the first time. More surprisingly, this broad-spectrum anticancer drug has “natural targeting” to tumor tissue.

 

What is disulfiram exactly?
In fact, it’s an alcohol deterrent, ordinary and cheap. How did it be found? It’s a long story, and you can find it in Science.

In the 1970s, an oncologist reported a “weird” case. A 38-year-old breast cancer patient with bone metastasis became a heavy drinker out of extreme sadness after diagnosis. The doctor stopped all the treatments and chose to give her an alcohol deterrent, for the sake of her last spending her spare time well.

However, to the doctor’s surprise, the patient ate and drank freely at home for nearly 10 years before finally falling to death because of drunkenness. Besides, autopsy also found there was no tumor tissue transferred to her bones.

Is it really drinking a cure for cancer? Or did disulfiram, this kind of anti-alcohol drug, unexpectedly work effectively? The above case aroused great interest of scientists and they conducted numerous clinical trials.

In 1993, a phase II clinical trial involving 64 non-metastatic high-risk breast cancers showed that combination chemotherapy with disulfiram, combined with chemotherapy alone, resulted in a 54% decrease in cancer recurrence and nearly 30% in death rate during the five-year follow-up period.



In 2015, a phase II clinical trial of 42 patients with stage IV non-small cell lung cancer showed that combination chemotherapy with disulfiram may increase the patient’s survival by 41% compared to chemotherapy alone. Meanwhile, two of the patients with advanced lung cancer who took disulfiram survived after a three-year follow-up, compared to two years in the placebo group.

However, why there is so few doctors dare to prescribe such anti-cancer drugs to patients for the time being? This drug features no patent protection and unclear anticancer mechanism, making the large pharmaceutical companies unwilling to perform the statutory Phase III clinical trials.

Later, a set of data studied for this surprise study showed amazing conclusions! Researchers selected health data for 240,000 newly diagnosed cancer patients in Denmark between 2000 and 2013, for a systematic analysis. They found that those who still in heavy alcohol abuse and treated with disulfiram, prolonged 34% more survival, compared to those who stopped drinking and using disulfiram after they were diagnosed with cancer.

Almost one century history of using guaranteed the safety of disulfiram. How does this ancient anti-alcohol drug exert anticancer activity? The explanation can be a little professional, which involves the protein balance within the cell. Under normal circumstances, intracellular protein synthesis is not flawless. Sometimes, part of the synthesis may be wrong, or its three-dimensional structure is not correct. Cell death eventually happens after the accumulation of these abnormal proteins. Here we need the help from the intracellular ubiquitin protease system, p97-NPL4.

This pathway is mainly responsible for the “quality control” of intracellular proteins. Once a “defective product” is found, these unwanted proteins are actively degraded. Especially in cancer cells, protein synthesis speed is very fast results from the accelerated cell cycle, resulting in more “defective products”. Therefore, the growth and survival of cancer cells are more dependent on the P97-NPL4 pathway for “quality control” of the protein.

Previous studies have also shown that significant activation of the p97 pathway is closely related to the growth and metastasis of a variety of cancers.


(Protein needs normal structure to function.  Photo shows DNA helicase)

A team led by Professor Jiri Bartek from Denmark found that metabolites of disulfiram in the body would bind to copper ions, forming an active anticancer complex that binds strongly to the NPL4 protein in the p97-NPL4 pathway. This combined complex inhibited the “quality control” function of the protein, making accumulation of a large number of residual proteins in cancer cells, and ultimately induced apoptosis of cancer cells.

In this experiment, Professor Bartek also verified the anti-cancer activity of disulfiram and found that disulfiram indeed significantly inhibited the growth of breast cancer and melanoma cells in mice, greatly prolonging the survival of mice.


Disulfiram (purplish red) significantly prolongs the life of melanoma mice

Well, there comes a question: the normal cells also need p97 for “quality control”, so will high-dose anti-cancer drugs bring serious side effects?

In mouse experiments, Professor Bartek also found that although “quality control” of protein in the normal cells cannot work without the participating of p97, but after feeding mice with disulfiram and copper ions, the metabolites of disulfiram should show “natural targeting” on tumors tissue.

We can see the metabolite is mainly concentrated in tumor tissue, with a tenfold higher concentration in tumor tissue than normal peripheral tissues and blood.

This discovery, figures out the specific mechanism of disulfiram’s anti-cancer activity, as a “century-old drug”. It also laid the foundation for the clinical application of disulfiram.

Currently, the researchers are planning to conduct three clinical trials, including treating metastatic breast cancer, colon cancer and glioblastoma combined with disulfiram.

Professor Bartek said: “This drug will hopefully save countless cancer patients around the world.”

Cancer treatment is always a hard nut to crack all over the world. For this splendid improvement in the cancer research, do you thumb you finger up or just stand as an onlooker?

 

 

 

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* The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.