Why tumors become resistant to chemotherapy?

December 2, 2013, IDIBELL-Bellvitge Biomedical Research Institute
This is a microscopic image of a colon cancer. Credit: PEBC

A common observation in oncology is the phenomenon that a patient with a tumor receives a drug and responds very well, but after a few months the cancer comes back and is now resistant to previously administered chemotherapy. What happened? Many mechanisms contribute to explain this effect called "acquired resistance", but today the group Manel Esteller, Director of Epigenetics and Cancer Biology at the Bellvitge Biomedical Research Institute (IDIBELL) , ICREA researcher and Professor of Genetics at the University of Barcelona, describes in the official Journal of the National Cancer Research Center in the United States , The Journal of The National Cancer Institute, the existence of epigenetic differences that explain the lack of response of the tumor recurs.

"We studied cells that were initially sensitive to oxaliplatin drug and then became insensitive to this drug and we found that resistant tumors had inactivated a gene (SRBC) in their DNA" says Manel Esteller "the loss of activity supposedly happens in a gene involved in DNA repair. Thus these , when receiving the drug, quickly repair the effect thereof and do not die. Studying nearly two hundred patients with colon cancer also found that inactivation of the gene is associated with poorer survival of these people despite treatment. Interestingly the loss of function of this gene could also explain why some are resistant from the outset, what is known as "primary resistance " concludes Esteller.

The discovery could have important implications for personalized treatment of colon cancer. If these findings extend to other clinical trials, determining the activation state of the SRBC gene could be useful in deciding whether a patient should receive a type of drug or another. Likewise the use of another class of drugs that return gen activity (epigenetic drugs) could restore the sensitivity to the original drug , oxaliplatin .

Finally, a very promising door is opened to examine whether similar mechanisms are happening in other human tumors beyond colon cancer.

Explore further: An epigenetic difference in twins explains different risk of breast cancer

More information: Epigenetic Inactivation of the BRCA1 Interactor SRBC and Resistance to Oxaliplatin in Colorectal Cancer. Moutinho C, Martinez-Cardús A, Santos C, Navarro-Pérez V, Martínez-Balibrea E, Musulen E, Carmona FJ, Sartore-Bianchi A, Cassingena A, Siena S, Elez E, Tabernero J, Salazar R, Abad A, Esteller M. The Journal of the National Cancer Institute, PMID: 24273214, 2013.

Related Stories

An epigenetic difference in twins explains different risk of breast cancer

October 17, 2012
Monozygotic twins have the same genome, that is, the same DNA molecule in both siblings. Despite being genetically identical, both twins may have different diseases at different times. This phenomenon is called "twin discordance". ...

Biologists ID new cancer weakness

November 14, 2013
About half of all cancer patients have a mutation in a gene called p53, which allows tumors to survive and continue growing even after chemotherapy severely damages their DNA.

Epigenetics emerges powerfully as a clinical tool

September 12, 2012
A study coordinated by Manel Esteller, published in Nature Reviews Genetics, highlights the success of this area of research to predict the behavior and weaknesses of tumors.

Researchers complete the first epigenome in Europe

May 30, 2012
A study led by Manel Esteller, director of the Epigenetics and Cancer Biology Program at the Bellvitge Biomedical Research Institute (IDIBELL), professor of genetics at the University of Barcelona and ICREA researcher, has ...

New study could enhance treatments for drug-resistant melanoma

November 21, 2013
Melanoma is the deadliest form of skin cancer, killing more than 8,000 in the U.S. each year. Approximately 40 percent of advanced melanoma tumors are driven to grow by the presence of mutations in a gene known as the BRAF ...

Recommended for you

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

Presurgical targeted therapy delays relapse of high-risk stage 3 melanoma

January 17, 2018
A pair of targeted therapies given before and after surgery for melanoma produced at least a six-fold increase in time to progression compared to standard-of-care surgery for patients with stage 3 disease, researchers at ...

Dulling cancer therapy's double-edged sword

January 17, 2018
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.

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.