APR 14, 2015 10:28 AM PDT

Central Signaling Pathway in Lymphoma Blocked Successfully

WRITTEN BY: Ilene Schneider
Cancer researchers from the University of Zurich have identified a key signaling pathway in B-cell lymphoma, a malignant type of blood cancer. They demonstrate that the signaling path-way can be blocked using compounds that are already in clinical development. This finding might be extremely important for the diagnosis, prognosis and treatment of this disease in the future.
A research group headed by Corina Schmid and Anne Müller from the Institute of Molecular Cancer Research at the University of Zurich has now identified a new signaling pathway that is active in and crucial for DLBCL cells.
Diffuse large B-cell lymphoma (DLBCL) is a blood cancer and the most common malignant condition of the lymphatic system. Although DLBCL is always fatal if left untreated, the cure rate after chemotherapy combined with antibodies approaches 60 to 70 percent. Certain types of DLBCL, however, do not respond well to this standard treatment, which results in a very poor prognosis for the patients. As the biology of this type of lymphoma remains poorly understood, there is a lack of targeted therapeutic approaches. A research group headed by Corina Schmid and Anne Müller from the Institute of Molecular Cancer Research at the University of Zurich has now identified a new signaling pathway that is active in and crucial for DLBCL cells - and can be attacked efficiently using substances that are already in clinical development for other diseases.

Prognosis factor for long-term survival

The UZH researchers based their experimental approach on the hypothesis that not only genetic, but also epigenetic changes might play a crucial role in the development of lymphoma. Consequently, they analyzed the so-called methylation of DNA, an epigenetic change that controls the activity of many human genes across the genome. Altered DNA methylation is a common feature of a wide variety of tumor types, which is why it seemed likely that lymphoma cells might also use this regulatory mechanism to their advantage.

And sure enough: The bioinformatical analysis of the methylation profilesof around 70 patient samples revealed eight regions on the DNA, so-called gene loci, that were all abnormally hypermethylated and turned out to be important for the cells' survival. "Follow up experiments revealed one locus in particular that is blocked in almost all the lymphoma patients examined due to DNA methylation and therefore cannot be translated into protein," sums up principal investigator Müller.

Moreover, the cancer researchers made an astonishing discovery: In several large patient cohorts, the epigenetic silencing of this gene locus proved to be an extremely significant, negative prognostic factor for the long-term survival of DLBCL patients. "This factor could thus be important for the diagnosis and prognosis of the disease, as well as therapeutic decisions in the future," said Müller.

Inhibitors effective

The newly identified gene locus contains the genetic information for an enzyme, a phosphatase, which regulates an important signaling pathway in the lymphoma cells and is evidently essential for the tumor cells to survive. Inhibitors are under clinical development for this signaling pathway. First author Schmid and principal investigator Müller were now able to demonstrate that these are also effective against lymphoma cells in cell cultures and in an animal model: Lymphomas in mice treated with the compound grew considerably more slowly than those in untreated mice. "Interestingly, combination therapies with other established substances proved especially effective," explains Schmid, "which makes the newly described signaling pathway a promising target for future cancer treatments."

Source: University of Zurich
About the Author
  • Ilene Schneider is the owner of Schneider the Writer, a firm that provides communications for health care, high technology and service enterprises. Her specialties include public relations, media relations, advertising, journalistic writing, editing, grant writing and corporate creativity consulting services. Prior to starting her own business in 1985, Ilene was editor of the Cleveland edition of TV Guide, associate editor of School Product News (Penton Publishing) and senior public relations representative at Beckman Instruments, Inc. She was profiled in a book, How to Open and Operate a Home-Based Writing Business and listed in Who's Who of American Women, Who's Who in Advertising and Who's Who in Media and Communications. She was the recipient of the Women in Communications, Inc. Clarion Award in advertising. A graduate of the University of Pennsylvania, Ilene and her family have lived in Irvine, California, since 1978.
You May Also Like
SEP 11, 2020
Cancer
Targeting Senescence in the Peripheral Nervous System to Fight Toxicity
SEP 11, 2020
Targeting Senescence in the Peripheral Nervous System to Fight Toxicity
Chemotherapy is a life-saving discovery for cancer patients. One of its biggest drawbacks is the toxicity that comes wit ...
SEP 25, 2020
Clinical & Molecular DX
Ray of Hope: Rare Cancer Biomarker Discovered
SEP 25, 2020
Ray of Hope: Rare Cancer Biomarker Discovered
Biliary tract cancer, or BTC, isn’t as talked about as breast or prostate cancers, probably because its incidence ...
NOV 02, 2020
Cancer
Using an Anti-Malarial Drug to Fight Cancer
NOV 02, 2020
Using an Anti-Malarial Drug to Fight Cancer
Modern pharmaceutical companies spend billions of dollars and years of time developing the next big drug. What if they d ...
NOV 09, 2020
Cancer
A Prognostic Expression Profile for Osteosarcoma
NOV 09, 2020
A Prognostic Expression Profile for Osteosarcoma
Tireless research goes into every cancer diagnostic tools and new therapy. Many types of cancer have made giant steps fo ...
NOV 15, 2020
Genetics & Genomics
Novel Cancer-Driving Genes are Discovered
NOV 15, 2020
Novel Cancer-Driving Genes are Discovered
Cells have to be able to divide so new ones can replenish cells that get worn out, dysfunctional, or that accumulate dam ...
NOV 18, 2020
Cancer
Could Targeting the Proteasome be Effective Against Cancer?
NOV 18, 2020
Could Targeting the Proteasome be Effective Against Cancer?
One of the trickiest things about anti-cancer drug design is targeting. Today, most drugs on the market target critical ...
Loading Comments...