This topic contains 13 replies, has 10 voices, and was last updated by daisychain 11 years, 1 month ago.
Interesting insights into why some components of myeloma manage to evade the treatment process and ensure disease progression.
http://medicalxpress.com/news/2013-09-cancer-root-multiple-myeloma-relapse.html
Clinical researchers at Princess Margaret Cancer Centre have discovered why multiple myeloma, an incurable cancer of the bone marrow, persistently escapes cure by an initially effective treatment that can keep the disease at bay for up to several years.
The reason, explains research published online today in Cancer Cell, is intrinsic resistance found in immature progenitor cells that are the root cause of the disease – and relapse – says principal investigator Dr. Rodger Tiedemann, a hematologist specializing in multiple myeloma and lymphoma at the Princess Margaret, University Health Network (UHN). Dr. Tiedemann is also an Assistant Professor in the Faculty of Medicine, University of Toronto.
The research demonstrates that the progenitor cells are untouched by mainstay therapy that uses a proteasome inhibitor drug ("Velcade") to kill the plasma cells that make up most of the tumour. The progenitor cells then proliferate and mature to reboot the disease process, even in patients who appeared to be in complete remission.
"Our findings reveal a way forward toward a cure for multiple myeloma, which involves targeting both the progenitor cells and the plasma cells at the same time," says Dr. Tiedemann. "Now that we know that progenitor cells persist and lead to relapse after treatment, we can move quickly into clinical trials, measure this residual disease in patients, and attempt to target it with new drugs or with drugs that may already exist. Dr. Tiedemann talks about his findings in this video:
In tackling the dilemma of treatment failure, the researchers identified a cancer cell maturation hierarchy within multiple myeloma tumors and demonstrated the critical role of myeloma cell maturation in proteasome inhibitor sensitivity. The implication is clear for current drug research focused on developing new proteasome inhibitors: targeting this route alone will never cure multiple myeloma.
Dr. Tiedemann says: "If you think of multiple myeloma as a weed, then proteasome inhibitors such as Velcade are like a persnickety goat that eats the mature foliage above ground, producing a remission, but doesn't eat the roots, so that one day the weed returns."
The research team initially analyzed high-throughput screening assays of 7,500 genes in multiple myeloma cells to identify effectors of drug response, and then studied bone marrow biopsies from patients to further understand their results. The process identified two genes (IRE1 and XBP1) that modulate response to the proteasome inhibitor Velcade and the mechanism underlying the drug resistance that is the barrier to cure.
Dr. Tiedemann is part of the latest generation of cancer researchers at UHN building on the international legacy of Drs. James Till and the late Ernest McCulloch, who pioneered a new field of science in 1961 with their discovery that some cells ("stem cells") can self-renew repeatedly.
The science has continued to advance unabated ever since, and notably with key discoveries by Dr. John Dick of cancer stem cells first in leukemia and next in colon cancer. Dr. Tiedemann's new findings underscore the clinical importance of understanding how cells are organized in the disease process.
That sounds like pretty good news Tom. Lets hope something comes from this by the time we relapse from our recent stem cell transplants. Hope you are still on the mend. It does take a while as I'm finding out.
Keep fighting.
Scott
Scott, day by day.
The last couple of weeks I'm feeling much more myself and plan a limited return to work at the end of the month. It gets easier.
Are you home yet?
Well here's hoping, if not for us because of the time it takes to complete research, produce a drug, have it tested then accepted but for the future generations who will have it.
Tom – this is what has happened to me. I've had six months of 'apparent' but very debilitating treatment with Velcade. I went down to a complete response for a month and then immediately my paraproteins started growing. My other treatments were steroids and cycloph.
We will have to find another strategy, possibly an immediate salvage transplant.
I'd like to stress that some patients do have much more sustained responses on Velcade. I will be having a bone marrow biopsy and a PET/CT scan in the next couple of weeks to check what's really happening, as I'm also quite a low secretor.
Thanks for the links. I will print the first one out and show it to my oncologist.
Good luck with you recovery.
Eva
Hi all
Looks good and reads well Thanks Young Tom 😀
Tom Onwards and Upwards
Hi Tom
Sorry but I think this has been around a few years!!!,this is we're you get the high risk Myelomas around 15 percent,that respond well to treatment,then as soon as it stops,it starts all over again. They have known about these people and there DNA for a long time.
This is why maintenance became an important weapon to buy more time.
We need more trials on the high risk who hardly get any remission,and there Myeloma gets harder to detect,they know what causes it,but in the UK they have to be treated with Chemo that NICE declares for Myeloma,also when patients become Non Secretor they often become uneligibal for trials as there is no way to monitor them!!! In the states people are being treated after DNA has been taken and best treatment agreed.
The new trials will give Dai and Eva a chance if they are eligible .CDP.Eve
Thanks Tom,
Love it when people post current research (I never seem to come across it on the net myself). I find it comforting that in say 10-20 yrs people who get it will get a much easier deal as it does concern me that my daughter may have genetic links – regardless of what they say. Am probably going down the SCT route – which I desperately want regardless of risks – but am sure in years to come they will see this as crude and barbaric (a bit like how we view medical practices in the middle ages) However, its all we've got at the moment and I will be grateful to get it.
Glad to hear your recovery is going well.
Stay well and keep posting please.
Rebecca
I think this is new research Eve. This specifically deals with relapse in the round not just for higher risk patients and it looks at why proteasome inhibitors are eventually surpassed. I think it's important stuff and the fact that it is already going into clinical trials and may be amenable to existing treatments is very promising.
Thanks for the info Tom. Hopefully it won't be too long till they find a cure.
Maureen
Yep. I've been home a couple of weeks now and very slowly on the mend. It does indeed take time.
Cheers
Scott
Hi Tom
You could be right!!! Hope you are,will watch for further details!!!
How are you starting to recover,it just takes time,and I wish you many many years,out of this Myeloma bubble.Eve
Thank you Tom for the information, this is great 😀 San x
Thanks Tom for the blog and links
Dawn x
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