Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Cancer Researchers Discover Root Cause of Multiple Myeloma Relapse

Published: Thursday, September 12, 2013
Last Updated: Thursday, September 12, 2013
Bookmark and Share
Clinical researchers have discovered why multiple myeloma persistently escapes cure by an initially effective treatment.

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.

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.

The research was funded by the Canadian Cancer Society, the Molly and David Bloom Chair in Multiple Myeloma Research, the Arthur Macaulay Cushing Estate and The Princess Margaret Cancer Foundation.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,600+ scientific posters on ePosters
  • More Than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Researchers Discover New Approach to Treating Colorectal Cancer
Approach disarms the gene that drives self-renewal in stem cells that are the root cause of disease, resistance to treatment and relapse.
Thursday, December 05, 2013
Scientific News
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Detecting HIV Diagnostic Antibodies with DNA Nanomachines
New research may revolutionize the slow, cumbersome and expensive process of detecting the antibodies that can help with the diagnosis of infectious and auto-immune diseases such as rheumatoid arthritis and HIV.
Snapshot Turns T Cell Immunology on its Head
New research may have implications for 1 diabetes sufferers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
Cell's Waste Disposal System Regulates Body Clock Proteins
New way to identify interacting proteins could identify potential drug targets.
New Approach to Treating Heparin-induced Blood Disorder
A potential treatment for a serious clotting condition that can strike patients who receive heparin to treat or prevent blood clots may lie within reach by elucidating the structure of the protein complex at its root.
Horse Illness Shares Signs of Human Disease
Horses with a rare nerve condition have similar signs of disease as people with conditions such as Alzheimer’s, a study has found.
How a Molecular Motor Untangles Protein
Diseases such as Alzheimer’s, Parkinson’s and prion diseases, all involve “tangled” proteins.
Compound Doubles Up On Cancer Detection
Researchers have found that tagging a pair of markers found almost exclusively on a common brain cancer yields a cancer signal that is both more obvious and more specific to cancer.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos