Nav: Home

Scientists identify potential new treatment strategy for kidney cancer

November 13, 2018

Researchers have provided new insight on the mechanisms behind the development of clear cell Renal Cell Carcinoma (ccRCC), according to new findings published in eLife.

The study in human cells and mice could have implications for how we understand and treat ccRCC - a major subtype of human kidney cancer.

Kidney cancer is one of the top 10 causes of death from cancer in both men and women. Inactivation of the tumour suppressor gene VHL is the primary cause of ccRCC, which is the most frequently occuring subtype of the disease. Tumour suppressor genes slow down cell division, repair DNA mistakes, and tell cells when to die. Mutations or inactivation of these genes stop them from working properly, which can lead to uncontrolled cell growth and cancer development.

"The disabling of VHL is usually followed by mutations in other tumour suppressor genes that are involved in ccRCC, such as PBRM1 and KDM5C," says co-first author Lili Liao, Postdoctoral Fellow at Jefferson (Philadelphia University + Thomas Jefferson University) and researcher at the Sidney Kimmel Cancer Center - Jefferson Health, Philadelphia, US. "These secondary tumour suppressors each have their own unique functions and their mutations are associated with different survival risks, yet they all collaborate with VHL loss to promote cancer development. In this study, we wanted to investigate whether they share a common tumour suppressor pathway that might be implicated in future ccRCC treatment."

While probing the gene expression patterns (the processes whereby instructions within DNA are converted into messenger RNA), the research team found that VHL, PBRM1, KDM5C, SETD2 and BAP1 all regulate the interferon stimulated gene factor 3 (ISGF3) - a master regulator that is key to viral infection response.

"We also saw that ISGF3 is strongly tumour-suppressive in a xenograft mouse model of ccRCC, as its loss enables tumours to increase significantly in size," explains co-senior author Haifeng Yang, Assistant Professor at Jefferson and researcher at the Sidney Kimmel Cancer Center - Jefferson Health. "Conversely, boosting ISGF3 in human ccRCC cancer cells shrinks the tumours they form into tiny nodules."

After VHL inactivation, it is known that the hypoxia-inducible factor (HIF)2 alpha becomes constantly active. HIFs respond to decreases in oxygen levels available within cellular environments. "We found that HIF2 alpha triggers the activation of ISGF3, which acts as a brake for tumour growth," Yang continues. "This brake can be disabled by the loss of any of the secondary tumour suppressors, suggesting that this is a key negative feedback loop in ccRCC."

"It is surprising to see that so many major tumour suppressor genes in ccRCC share the same target in ISGF3," adds co-senior author Qin Yan, Associate Professor of Pathology at Yale University, Connecticut, US. "As many critical cancer genes in kidney cancer converge on ISGF3, it might play significant roles in drug development, patient responses to treatments, and survival."

"There is a significant unmet clinical need to develop new strategies for treating ccRCC. Dr. Yang's breakthrough study brings us one step closer to this goal," concludes Dr. Karen E. Knudsen, Enterprise Director of the Sidney Kimmel Cancer Center at Jefferson Health.
-end-
Reference

The paper 'Multiple tumor suppressors regulate a HIF-dependent negative feedback loop via ISGF3 in human clear cell renal cancer' can be freely accessed online at https://doi.org/10.7554/eLife.37925. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Media contact

Emily Packer, Senior Press Officer
eLife
e.packer@elifesciences.org">e.packer@elifesciences.org
01223 855373

About eLife

eLife aims to help scientists accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours in science. We publish important research in all areas of the life and biomedical sciences, including Cancer Biology and Chromosomes and Gene Expression, which is selected and evaluated by working scientists and made freely available online without delay. eLife also invests in innovation through open-source tool development to accelerate research communication and discovery. Our work is guided by the communities we serve. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, the Wellcome Trust and the Knut and Alice Wallenberg Foundation. Learn more at https://elifesciences.org/about.

To read the latest Cancer Biology and Chromosomes and Gene Expression research published in eLife, visit https://elifesciences.org/subjects/cancer-biology and https://elifesciences.org/subjects/chromosomes-gene-expression.

eLife

Related Cancer Articles:

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.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.