Research team uncovers root cause of multiple myeloma relapse

September 18, 2013

Researchers have discovered why multiple myeloma, a difficult to cure cancer of the bone marrow, frequently recurs after an initially effective treatment that can keep the disease at bay for up to several years.

Working in collaboration with colleagues at Princess Margaret Hospital in Toronto, researchers from Mayo Clinic in Arizona and the Translational Genomics Research Institute (TGen) in Phoenix were part of the team that conducted the study published in the Sept. 9 issue of Cancer Cell.

The research team initially analyzed 7,500 genes in multiple to identify genes which when suppressed made resistant to a common class of drugs called proteasome inhibitors such as bortezomib or carfilzomib. Then, the team studied bone marrow biopsies from patients to further understand their results. The process identified two genes (IRE1 and XBP1) that control response to the proteasome inhibitor and the mechanism underlying the that is the barrier to cure.

The findings showed recurrence was due to an intrinsic resistance found in immature tumor progenitor (mother) cells is the root cause of the disease and also spawns relapse. The research demonstrates that although the visible cancer cells that make up most of the tumor are sensitive to the proteasome inhibitor drug, the underlying progenitor cells are untouched by this therapy. These 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 at the same time," says Rodger Tiedemann, M.D., a specializing in multiple myeloma and lymphoma at Princess Margaret. "Now that we know that persist and lead to relapse after treatment, we can move quickly into clinical trials, measure this in patients, and attempt to target it with new drugs or with drugs that may already exist."

"Some myeloma cells are too immature to be caught by the drugs and thus hide underground only to reemerge later," says Keith Stewart, M.B., Ch.B., Dean for Research at Mayo Clinic in Arizona and contributor to the study. "This study has wide implications in the search for a cure of this common blood cancer as this 'progenitor cell' will have to be targeted."

Jonathan Keats, Ph.D., head of TGen's Multiple Myeloma Research Laboratory, said: "This study, which leverages data generated at TGen as part of the Multiple Myeloma Genomics Initiative, shows how mutations acquired by multiple myeloma tumors can make a tumor resistant to specific therapies and highlights the importance of TGen's precision medicine approaches."

Dr. Tiedemann says: "If you think of multiple myeloma as a weed, then proteasome inhibitors are like a goat that eats the mature foliage above ground, producing a remission, but doesn't eat the roots, so that one day the weed returns."

Explore further: Cancer researchers discover root cause of multiple myeloma relapse

More information: Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma, Cancer Cell, 2013.

Related Stories

Cancer researchers discover root cause of multiple myeloma relapse

September 9, 2013
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 ...

TGen professor discusses benefits of whole genome sequencing in study of multiple myeloma

April 3, 2013
The scientific benefits of whole genome sequencing at the Translational Genomics Research Institute (TGen) will be presented at the 14th International Myeloma Workshop, April 3-7 at the Kyoto International Conference Center.

Preclinical tests may lead to new approach to treat CNS lymphoma

August 12, 2013
A drug recently approved for use in multiple myeloma is now being tested for its ability to fight central nervous system (CNS) lymphoma, a deadly cancer of the immune system that can affect the brain, spinal cord and fluid, ...

Towards more effective treatment for multiple myeloma

January 9, 2012
A new study from SUNY Downstate Medical Center in Brooklyn, New York, shows that MAL3-101, a recently developed inhibitor of the heat shock protein 70 (Hsp70), appears to have potent anti-tumor effects on multiple myeloma, ...

Possible new therapy for the treatment of myeloma

September 5, 2012
(Medical Xpress)—Research from Karolinska Institutet shows that sorafenib, a drug used for advanced cancer of the kidneys and liver, could also be effective against multiple myeloma. The disease is one of the more common ...

Aggressive breast cancers may be sensitive to drugs clogging their waste disposal

August 12, 2013
In a new paper in Cancer Cell, a team led by Judy Lieberman, PhD, of Boston Children's Hospital's Program in Cellular and Molecular Medicine reports "triple-negative" breast cancers may be vulnerable to drugs that attack ...

Recommended for you

New study shows how cells can be led down non-cancer path

October 23, 2017
As cells with a propensity for cancer break down food for energy, they reach a fork in the road: They can either continue energy production as healthy cells, or shift to the energy production profile of cancer cells. In a ...

Microbiologists contribute to possible new anti-TB treatment path

October 23, 2017
As part of the long effort to improve treatment of tuberculosis (TB), microbiologists led by Yasu Morita at the University of Massachusetts Amherst report that they have for the first time characterized a protein involved ...

Major study of genetics of breast cancer provides clues to mechanisms behind the disease

October 23, 2017
Seventy-two new genetic variants that contribute to the risk of developing breast cancer have been identified by a major international collaboration involving hundreds of researchers worldwide.

Proton therapy lowers treatment side effects in pediatric head and neck cancer patients

October 23, 2017
Pediatric patients with head and neck cancer can be treated with proton beam therapy (PBT) instead of traditional photon radiation, and it will result in similar outcomes with less impact on quality of life. Researchers from ...

Big Data shows how cancer interacts with its surroundings

October 23, 2017
By combining data from sources that at first seemed to be incompatible, UC San Francisco researchers have identified a molecular signature in tissue adjacent to tumors in eight of the most common cancers that suggests they ...

Symptom burden may increase hospital length of stay, readmission risk in advanced cancer

October 23, 2017
Hospitalized patients with advanced cancer who report more intense and numerous physical and psychological symptoms appear to be at risk for longer hospital stays and unplanned hospital readmissions. The report from a Massachusetts ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.