Treating Cancer as Though It Were an Infectious Disease
Here researchers propose an interesting approach to destroying cancer stem cells via targeted antibiotics. Cancer stem cells have been shown to be the driving force behind many types of cancer: without their presence, tumors would halt their growth or wither. At this point cancer research as a whole is far too slow and expensive. Faster progress towards meaningful treatments will arise from identifying and focusing on common points of attack that are essentially the same in many different types of cancer. However all too many of today's expensive and time-consuming research programs are entirely specific to the genetics and cell metabolism of one very narrow subtype of cancer, and even then individual tumors of that subtype can evolve to remove the vulnerability in question. So it is worth keeping an eye on programs that might blossom into classes of therapy applicable to a broad swathe of cancers:
We propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect".Based on this analysis, we now show 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)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy.
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. Finally, recent clinical trials with doxycycline and azithromycin (intended to target cancer-associated infections, but not cancer cells) have already shown positive therapeutic effects in cancer patients, although their ability to eradicate cancer stem cells was not yet appreciated.
I have to greet this one with skepticism; surely with the use of antibiotics in hospital settings, particularly with all the risks of secondary infections from wounds caused by cancer and cancer surgery, someone would have noticed that a certain antibiotic does something to a certain kind of cancer by now...?
If this is actually real and not yet another wishful-thinking paper or outright fraud, oncologists everywhere are going to wonder why they didn't catch this.
@Slicer: Knowing the investigators' track record, I'm pretty confident that this is neither wishful thinking nor outright fraud. Your comment about the informal epidemiological sniff test is very sensible, but naturally there is the problem of confounding and this being standard of care: of course most people are going to do better with their cancer after receiving a successful round of antibiotics, because the control group will either be dead of the infection or the cancer, and an ongoing infection will in any case weaken the organism's ability to fight off the malignancy. Additionally, there actually is some clinical support for this, albeit also confounded by the same problem (here quoting from the paper):
My larger concern with the paper, in brief, is that I'm not very impressed with the criteria used to qualify cells as cancer stem cells in vitro or for the selective toxicity to such as an assay. I'm not going to pay this much mind absent stronger evidence, preferably in vivo.
@Slicer - also bare in mind that Cancer is often fairly heterogeneous, consisting of many cancer types, cell types, and even non cancerous cells recruited for their immune suppressing properties. Selectively killing one cell type that is highly resistant to regular chemotherapy or other treatments could have benefits. But like all cancer breakthroughs, don't get excited until it has been tested in a stage 2 clinical study.
I had sereos cancer tumor. I had a complete hysterectomy and chemotherapy. 16 months after I finished Chemotherapy my CA-125 skyrocketed! I was given 3-4 months without chemo. I started a chemo of Doxil, Carboplatin, and Avastin. I have a very poor prognosis. I got pneumonia while on Chemo. I was too sick for chemo and was given Azithromyacin for the lung infection. My cancer number dropped dramatically while on Azithromyacin. Azithromyacin was more effective at lowering my CA-125 than chemo. I am not the only person that had the same result with ovarian cancer. I am looking for others that had similar results. I want clinical trials for ovarian cancer. Good results have already been shown in lymphoma and lung cancer human trials. The antibiotics kill cancer stem cells in all cancer lines.