The dandelion phenomenon, part II

Picking up from where I left off yesterday, the first type of cancer to be linked to stem cells was chronic myeloid leukaemia, or CML. The Johns Hopkins researchers proceed with a lengthy discussion on a drug called imatinib, which is used in CML, but without much success in the long-term. CML patients relapse if they discontinue imatinib (which, the researchers tell us, is currently being used more than interferon-alpha or IFN), or their cancer progresses even while they are on it. There appears to be no survival advantage in taking imatinib. The explanation, the researchers suggest, may lie in the CML stem cell resistance to this drug.

They use the dandelion analogy: “This pattern of activity is analogous to cutting a dandelion off at ground level. Although this will eliminate the visible portion of the weed, the unseen root also needs to be eliminated to prevent regrowth of the weed.”

Contrary to what happens with imatinib, CML patients’ response to the above-mentioned IFN is slow and gradual, “but can be durable.” So IFN would appear to act against the CML stem cells. Then we read “Thus, treatments that selectively attack cancer stem cells will not immediately eliminate the differentiated tumor cells. In this situation, cure (elimination of the cancer stem cells) in effect precedes the clinical demonstration of complete remission (clearance of the differentiated cancer cells) and could occur without actual disease shrinkage.”

This explains why these researchers took such a strong stance against the above-mentioned theory of complete remission. Complete remission may last months or years, but the cancer will return, eventually, unless the cancer stem cells are targeted. A treatment that targets cancer stem cells, however, won’t necessarily affect the circulating non-stem cancer cells. Hence, in this scenario, cure occurs before complete remission. This is contrary to everything I have read on the myeloma patient listservs (where a lot of the focus is on complete remission, or CR as we write it) and in the official myeloma literature. There are heaps of studies on the importance of complete remission in myeloma, in fact.

The researchers go on to discuss bortezomib (marketed as Velcade), a proteasome inhibitor, and lenalidomide (marketed as Revlimid, a derivative of thalidomide) commonly used in the conventional treatment of myeloma. These two drugs “can inhibit myeloma plasma cells but appear to have little activity against myeloma stem cells in vitro,” which means that they are pruning only the visible part of the dandelion, whereas rituximab, a monoclonal antibody, targets myeloma stem cells, i.e., the dandelion’s roots, according to the Johns Hopkins team.

The danger, the researchers point out, is that “As with IFN in CML and rituximab in myeloma, therapy directed against cancer stem cells might be prematurely abandoned if clinical activity is judged solely by criteria that reflect the effects of treatment on the bulk of the cancer.” And in fact, they add,“Not surprisingly, rituximab was found to have limited activity against myeloma in a short-term clinical trial. Rituximab’s activity against myeloma stem cells probably could not have manifested as immediate clinical responses in this trial because of the persistence of the long-lived, but terminally differentiated, myeloma plasma cells.” There you go.

So when we target stem cells, we must be patient. Unfortunately, nowadays, patience is no longer a virtue. We want to see immediate results. Overnight.

The researchers suggest setting up a clinical trial using bortezomib against the bulk of the cancer cells and then rituximab against the myeloma stem cells. Almost two years and a half have passed since this study was published. I went to have a look at the clinical trials being conducted right now. There are 591 trials (!) testing rituximab. I narrowed my search to myeloma, and found that there are 18 trials using rituximab alone or in combination with other drugs, such as lenalidomide or melphalan. Only one study, at the Dana-Farber Cancer Institute, is being conducted with rituximab and bortezomib, but for patients with Waldenstrom’s macroglobulinemia.

Well, these are certainly interesting times. I am all in favour of the dandelion theory, and it is for that reason that I am monitoring the DMAPT clinical trial, which should be beginning soon. (I admit to being more interested in substances such as DMAPT than in rituximab.)

The trees that are slow to grow bear the best fruit. (Molière)


  1. Gluten-free vanilla… I’m not sure if all vanilla is. I was given a bottle of organic vanilla from Madagascar.. that the giver says is gluten-free. I found on the internet both the information that you should be sure to get gluten-free.. and the information that all vanilla is gluten-free. I guess I really don’t have a clue after all.
    Thanks always for your insightful work.

  2. Hi there, a lot of interesting information, many thanks for decoding it Margaret.

    I have been following up my thoughts on Adrenal glands, stress etc. I think I mentioned that I was looking at a Now product that contained Honokiol and Berberine. Guess what, they are marketing it as an anti stress supplement, which helps stablise cortisol and so stops sudden bursts of adrenal, it’s called Relora(which has actually got a pantent pending for Next Pharmaceuticals, who make it) I have done several searches and they all look very interesting I have attached a link which discusses it’s attributes and safety, see pages 1, 12 & 13 although there are some other very interesting articles as well. Just a paragraph to get you interested, does anyone reconise any of these symptoms, I could tick everyone.
    “Too much cortisol causes
    abdominal obesity, high blood sugar
    (“adrenal diabetes”), muscle wasting, bone
    loss, immune shutdown, brain (hippocampus)
    atrophy, poor wound healing, thin wrinkled
    skin, fluid retention and hypertension”.
    Another link of study done in 2007
    I have thought for quite some time that MM messed up the Adrenal glands and those parts that fed to or from them, but my doctors didn’t want to listen. I feel this makes a lot of sense and what with all the new studies that confirm Honokiol causes apoptosis to MM cells, and another study I found on Phellodendron amurense bark (berberine) in a product called Nextrutine also by Next Pharmaceuticals, it Modulates Cox-2 !!
    I am definately going to ask my doctor to do my bloods earlier and get some relora and do my own mini study, probably combining it with Curcumin. By the way it suggests somewhere that it shouldn’t be taken with alcohol, but does’n’t say why.
    What do you think Margaret.

    Hope you don’t mind me putting this on your blog


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