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Tuesday 20 February 2018
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Groundbreaking research shows antibiotics could have a key role in cancer therapy

by Justina Hurley

antibiotics kill cancer cells

And it was inspired by the clever thinking of an eight year old girl

A UK cancer research team based in Manchester at the Breakthrough Breast Cancer Research Unit, have produced some ground breaking research into a very simple form of cancer treatment that just might work, namely, antibiotic therapy.

How it began – the wisdom of a child.

When husband and wife cancer research team, Professor Michael Lisanti (Professor of Cell Biology and Director of the Breakthrough Breast Cancer Research Unit, Manchester, UK) and Dr Federica Sotgia (Manchester Institute of Cancer Sciences) were discussing cancer at home, they asked their eight year old daughter Camilla what she thought might cure cancer. She suggested that it could be antibiotics, like when she has a sore throat.

Rather than dismiss her idea out of hand they decided to test it. Professor Lisanti had a small growth on his face and applied some antibiotic cream to it. The growth disappeared. They then went on to test the antibiotics further in the lab and discovered to their amazement that several cheap and commonly prescribed antibiotics killed cancer cells.

Several months later and they have produced a groundbreaking paper: Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease and young Camilla is listed in the credits.

The premise of their research is that as each patient’s tumour is “fairly unique in its complexity of genetic changes and that several divergent cancer cell clones may also co-exist, within a single tumour, this genetic complexity makes it extremely difficult to design new diagnostics and targeted-therapeutics, to achieve the goals of personalized medicine.”

What this means in effect is that cancer is not a one size fits all disease and each person can have a different variety or several different varieties of cancer unique to them.

The alternative approach is to find something common to all cancers and work on that. The alternative approach they found was that one common target that may be easier to manage is the property of “stemness” in cancer cells.

What is stemness?

In biology a stem cell has the ability to turn into any kind of cell in the human body. Studies of cancer cells have found that they also have a stem cell type property and this is called “stemness”. For more on this see this study on Cancer, Stemness and Cancer Stem Cells.

The strategy this team propose is to target the stemness and  they identified a weak point in cancer which was a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells.

So what is mitochondrial biogenesis?

The mitochondria are the energy powerhouses of a cell and mitochondrial biogenesis is in essence the process that describes how new mitochondria are formed in the cell.

cancer antibiotic breakthrough

Think of a cell as like a little house with its own occupants and its own power supply. The nucleus of the cell contains the DNA which describes what that cell is to be – for example a skin cell, a muscle cell, a heart cell. The mitochondria are not in the nucleus but are contained in the elements of the whole cell and are responsible for the power supply and for regulating the cell life cycle, growth and for regulating cell death. The mitochondria also contain their own independent DNA and their DNA is very similar to bacterial genomes.

As the mitochondria are involved in apoptosis, which is programmed cell death and cancer is ultimately a failure of apoptosis to occur, this is why the Manchester team hit upon the need for the production of mitochondria for cancer stem cells to grow and survive.

So what does this have to do with antibiotics?

Well a common side-effect of  several classes of FDA-approved antibiotics is that they actually inhibit mitochondrial biogenesis. The team decided to look at this in reverse and view the side effect instead as a therapeutic effect.

For example, they quote the results of recent clinical trials that used antibiotics to treat cancer related infections and which increased patient survival in one case and led to remission in another. Neither trial was focusing on cancer as a therapy and so the connection was not made in those trials that it was the antibiotic use in itself that led to the positive results:

Recent clinical trials with doxycycline and azithromycin (intended to treat cancer-associated infections, but not cancer cells) both show positive therapeutic effects in cancer patients, although their selective effects on eradicating cancer stem cells were not yet known or appreciated [2326]. These trials were performed on advanced or treatment-resistant patients with B-cell lymphoma (doxycycline) or lung cancer (azithromycin), respectively [2326]. For example, in lung cancers, azithromycin significantly increased 1-year patient survival from 45% to 75%, an ~1.7-fold increase [26]. Interestingly, it was noted that even lymphoma patients that were “bacteria-free” benefited from only a 3-week course of doxycycline therapy, and showed complete remission of the disease [27]. These results suggest that the antibiotic’s therapeutic effects were actually infection-independent.

Following their study focusing on a therapeutic use of antibiotics to act against cancer stem cells, they found that “4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)).”

cancer cell lines

These five classes of mitochondrially-targeted antibiotics included: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol.

What is most important is that as antibiotics are already in use in people, it is known that many of these drugs are non-toxic for normal cells, and this is likely to reduce the side effects of anti-cancer therapy.

Their final analysis:

“Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis.”

This is a very promising and exciting study and we will keep a close eye on their progress.

Sources: 

Lamb, R., Ozsvari, B., Lisanti, C., Tanowitz, H., Howell, A., Martinez-Outschoorn, U., Sotgia, F., & Lisanti, M. (2015). Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease  Oncotarget, 5

Background story: Has girl of eight found a cancer cure? Scientist parents discover antibiotics can kill cells after their daughter suggested they try it over the dinner table  The Daily Mail Jan 29th 2015

 

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