There are times in Medicine when an idea seems so simple, so obvious, that it couldn’t possibly work. Except when it does. Husband and wife cancer research team, Drs. Michael Lisanti and Federica Sotgia, asked their 8 year-old daughter one evening at the dinner table, “Camilla, how would you cure cancer?” The little girl thought for a moment and then responded that she would use antibiotics, “like when I have a sore throat.”
Skeptical though they were, Drs. Lisanti and Sotgia gave it a try, exposing various cancer stem cell lines to different families of antibiotics. And to their remarkable surprise, it worked. Cancer cells were unable to spread in the face of antibiotic onslaught. But why?
Lisanti reports that it’s a well-known side effect for antibiotics to target the mitochondria in human and animal cells . His explanation for the success of these early trials is the fact that mitochondrial numbers tend to vary by cell according to the rate of the cell’s proliferation. Rapidly dividing cancer cells, for instance, have very large numbers of mitochondria because mitochondria supply necessary energy for the cell. Therefore, cancer cells are particularly vulnerable to mitochondrial impairments and thus antibiotic exposure. Stopping it from creating more mitochondria stops a cancer cell in its mitotic tracks.
Lisanti and his team studied 5 different classes of antibiotics which are known to target mitochondria. Each of these classes acts by inhibiting protein synthesis in mitochondria through different targets (e.g., the 39S large mitochondrial ribosome versus the 28S small mitochondrial ribosome, etc.), while leaving protein synthesis in the cytoplasm of the cell unaffected. They found, for instance, that the broad-spectrum antibiotic, doxycycline, inhibited tumor-sphere formation across a variety of different cancer types tested, including breast, ovarian, lung, melanoma, prostate, and pancreatic cancers.
Currently, there are two clinical trials initiated or ongoing to test the efficacy of antibiotic use on cancer treatment. One clinical trial, which has already moved into Phase 2, is testing doxycycline use on advanced breast cancer and bone metastasis. And another study, which is still currently recruiting patients, is testing doxycycline use in relapsed patients with non-Hodgkin’s lymphoma, which can be accessed here for anyone interested.
It’s uncertain at this stage whether antibiotics provide a potential cure or whether they may simply pause the progression of the disease. Azithromycin use in lung cancer patients, for example, improved length of survival. Meanwhile, lymphoma patients following a 3-week course of doxycycline treatment experienced complete remission of their disease. The answer therefore may be “either”, depending on the type of cancer and the stage of progression.
Thank you, Emily, for yet another opportunity to learn something fascinating! It also makes me think of the surprise that greeted suggestion of possible association between minocycline and some psychiatric and neurodevelopmental symptoms.
I think maybe I should have said “symptom improvement.” Anyway, I love the story of the eight-year-old girl’s suggestion.
Glad you enjoyed it. A student of my husband had run across the story and linked me to it. I thought it sounded fascinating and potentially very promising. Let’s hope it ends up being as effective as the laboratory studies suggest!
I wasn’t familiar with the previous work on minocycline and schizophrenia before you mentioned it. I did a little brief reading. Like doxycycline, it’s also part of the tetracycline family of antibiotics, which Lisanti writes in his article all appear to inhibit function of the small subunit of the mitochondrial ribosome. Presumably, some of its usefulness in curbing positive and negative symptoms in schizophrenia may lie in its regulation of mitochondria. Perhaps some of the aberrant processes of schizophrenia involve cellular growth (e.g., reparative sprouting) and inhibiting mitochondrial biogenesis impairs that growth. Just a thought, a common theme I’m noticing to many of the neurodevelopmental conditions.
Thanks for the info. 🙂
Thanks for explaining about this common theme connected to multiple disorders. Speaking of multiple disorders, minocycline has been studied to some degree in obsessive compulsive disorder, autism, fragile X and (as you pointed out) connected to negative and positive schizophrenia symptoms. Authors of these studies have talked about things including neuroprotective properties and potential effects on glia and mitochondria.
Thank you for informing about the Lisanti article. I’m still working on pulling up full text on my computer, but I’m happy to find that pubmed lists it as free. : )