Cracking the case of the century, Danish-Czech-U.S research team figures out why a 1970s alcoholic died with her cancer mysteriously in remission.
She wasn’t always an alcoholic. But when she was 38, her cancer had spread from her breast tissue into her bones. It was then she began turning to alcohol for solace. Her doctors had no choice but to discontinue her cancer treatment, instead, prescribing her an anti-alcohol addiction medication and placing her into psychiatric care. But it just wasn’t enough.
In 1971 – about ten years after her cancer diagnosis – she died falling off a third-floor window, drunk and intoxicated.
The case was documented in the 1976 National Institute Cancer Monograph by Dr. Edward Lewison, the founder of the John Hopkins breast clinic. The patient’s name left out of the manuscript for privacy reasons, but Lewison couldn’t help but be strangely drawn to the story: not because of her tragic demise, but rather that despite not receiving any form of cancer therapy during her last ten years, she died with her cancer mysteriously in remission.
In her autopsy, the coroner found no obvious traces of cancer on her spine, skull, pelvis, or ribs, and could only tell that she had been a cancer patient from the several small residual nests of metastatic carcinoma hidden in her bone marrow.
The only clue in the case – she was prescribed the drug “disulfiram”
Disulfiram, also sold under the trade name Antabuse, is commonly used to support the rehabilitation of alcoholics by increasing their sensitivity to alcohol. The drug inhibits a key enzyme in the alcohol detoxification process that leads to ethanol – and its toxic byproducts – to accumulate in the body. This leads to chest pains, vomiting, and headaches. By creating these effects every time the patient drank alcohol, physicians use Antabuse to help patients break the habit.
But what does an anti-alcohol addiction drug have to do with cancer? The second piece to this mystery lies in a 1993 clinical trial, where a team of French scientists began testing a separate – but related drug – ditiocarb. The drug was highly effective in increasing breast cancer patient survival and the researchers suspected a link between ditiocarb and Antabuse due to their chemical similarities. But because of the study’s small sample size and the fact that nobody at that time understood how the drugs worked, both studies were quickly forgotten.
Bringing two and two together – Antabuse is converted to ditiocarb after ingestion
It’s been almost 50 years, but the case was finally cracked when a Danish-Czech-U.S. research team decided to revisit the 1971 study, this time bringing with them an arsenal of modern scientific methods. By combing through over 240,000 cancer cases in Denmark’s cancer registry, the research team lead by Dr. Jiri Bartek, tracked down over 3000 patients who had taken Antabuse between 2000 and 2013. Their analysis found that the drug reduced cancer death rates by 34%. As Lewison had suspected back in the early 70s, it was Antabuse that killed the cancer, but what he couldn’t figure out back then was why.
When Bartek’s team tested the drug in mice they found that Antabuse halted the growth of breast cancer tumours – an effect that was further enhanced when their diet was supplemented with additional copper.
The researchers also found that when Antabuse was metabolized, ditiocarb is produced, which goes on to form a complex with copper in cancer cells. When bound to copper, ditiocarb blocks the machinery cells use to recycle malformed and unneeded proteins. As the waste builds up, it interferes with the cell’s other essential functions, eventually causing death.
Packing a punch – Combining Antabuse with existing anti-cancer therapies
While many other approved cancer drugs also interfere with the same protein clean-up process, Antabuse seems to be unique in that it only targets cancer cells. Bartek’s team isn’t sure why, but because normal cells aren’t harmed, patients can take Antabuse for years with little to no side effects. Bartek and collaborators now want to perform clinical trials using an Antabuse-copper combo to treat breast, colon, and brain cancers, but without enough funding, it might be difficult to make happen.
Most pharmaceutical companies won’t invest in this type of treatment because there’s no patent protection for Antabuse. The drug is already FDA approved and has been in the market for over 60 years. But if Bartek’s pending trials prove to be successful, Antabuse can be prescribed as an inexpensive addition to traditional anti-cancer therapies, giving oncologists the chance to land two hits for the price of one.