New possible target for cancer treatment

June 06, 2017

Scientists at Karolinska Institutet in Sweden report that cancer cells and normal cells use different 'gene switches' in order to regulate the expression of genes that control growth. In mice, the removal of a large regulatory region linked to different types of cancer caused a dramatic resistance to tumour formation, but did not affect normal cell growth. The findings, published in the scientific journal eLife, highlight the possibility of developing highly specific cancer drugs with fewer side effects.

Humans have close to 20,000 genes to carry out all the functions in a cell. The genes make up only 2 per cent of a cell's total DNA. What makes us different from one another is mainly the variation in the remaining 98 per cent of our DNA. The variation is believed to alter the activity of regulatory regions or 'gene switches' (enhancer elements), which control the activity levels of genes in a cell. It is this variation that is mainly responsible for making individuals more or less susceptible to the development of diseases such as cancer.

In the current study, using mice, scientists have analysed a large gene switch region that is linked to the risks of developing many different types of cancer, including prostate, breast, colon, bladder and thyroid cancers as well as chronic lymphocytic leukaemia and myeloma. The variation in this region accounts for far more cancer-related deaths than inherited mutations in well-known cancer-causing genes. It is currently unclear why cancer cells use these particular switches, and whether they have any function in normal cells.

The scientists turned the gene switches off by removing this region from the mouse genome, and found that its loss has no effect on normal mouse development and growth. Although removing the gene switch region brought down the levels of the nearby cancer gene Myc, the mice remained normal and healthy. However, the mice were strongly resistant to the formation of breast tumours and tumours in the intestine.

According to the scientists, these results show that normal cells can function and divide without the genetic elements that are needed for the growth of cancer cells. The study therefore highlights the possibility of developing highly specific cancer drugs.

"Since we find that the growth of normal and cancer cells is driven by different gene switches, we can in principle aim at switching off the system for growth only in the cancer cells without any harmful effect on the growth of normal cells. This can lead to the development of highly specific approaches for cancer therapy with much lower toxic side effects", says Professor Jussi Taipale at Karolinska Institutet's Department of Medical Biochemistry and Biophysics who led the study.
-end-
The work was supported by the Center for Innovative Medicine at Karolinska Institutet, the Knut and Alice Wallenberg Foundation and the EU FP7 Health project SYSCOL.

Publication: "Mice deficient of Myc super-enhancer region reveal differential control mechanism between normal and pathological growth", Kashyap Dave, Inderpreet Sur, Jian Yan, Jilin Zhang, Eevi Kaasinen, Fan Zhong, Leander Blaas, Xiaoze Li, Shabnam Kharazi, Charlotte Gustafsson, Ayla De Paepe, Robert Månsson and Jussi Taipale, eLife online 6 June 2017.

Karolinska Institutet

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.