Reviewed by Emily Henderson, B.Sc.May 20 2020
"Senotherapy," a treatment that uses small molecule drugs to target "senescent" cells, or those cells that no longer undergo cell division, blunts liver tumor progression in animal models according to new research from a team led by Celeste Simon, Ph.D., a professor of Cell and Developmental Biology in the Perelman School of Medicine at the University of Pennsylvania and scientific director of the Abramson Family Cancer Research Institute. The study was published in Nature Cell Biology.
This kind of therapy is not something that has been tried before with liver cancer. And in our models, so-called 'senolytic' therapy greatly reduced disease burden, even in cases with advanced disease."
Celeste Simon, Ph.D., Professor of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania
Loss of the enzyme FBP1 in human liver cells significantly increases tumor growth. Previous research has shown FBP1 levels are decreased in stage 1 tumors, and further reduced as the disease progresses. In this study, Simon and her team used RNA-sequencing data to identify FBP1 as universally under-expressed in the most common form of liver cancer, hepatocelluar carcinoma, regardless of underlying causes like obesity, alcoholism, and hepatitis.
The loss of FBP1 in liver cells activates the neighboring hepatic "stellate cells"--which make up ten percent of liver mass--causing fibrosis (tissue scarring) and subsequent stellate cell senescence, both of which promote tumor growth. Researchers found that these senescent stellate cells can be selectively targeted by senolytics, including Navitoclax (already in clinical trials for other diseases, like hematological malignancies), in order to blunt tumor progression driven by liver cell-specific FBP1 loss.
The team provides the first genetic evidence for FBP1 as a bona fide metabolic tumor suppressor in the liver and that its loss in liver cells promotes the growth of tumors because of effects on other cells within the tumor microenvironment.
Using genetically engineered mouse models, the team eliminated FBP1and found the disease progressed more rapidly and tumor burden greatly increased in carcinogen-mediated, dietary, and other forms of hepatocellular carcinoma.
"The case with liver cancer is very dire, once you get beyond a certain stage there are limited, if any, treatments available," Simon said. "As obesity rates continue to increase and viral infections continue to be a problem, there is going to be an increasing surge of liver cancer which currently has few treatment options. And since FBP1 activity is also lost in renal cancer, FBP1 depletion may be generally applicable to a number of human cancers. What's unique about our senotherapy approach is that we are specifically targeting other cells in the liver tumor environment rather than the cancer cells themselves."
Next steps, according to researchers will be to begin to test these treatments in a clinical setting.
Excerpt from:
'Senolytic' therapy blunts liver tumor progression in animal models - News-Medical.Net
- Close Encounters of Skin and Nerve Cells - The Scientist - April 15th, 2024 [April 15th, 2024]
- OrthoID: Decoding Cellular Conversations with Cutting-Edge Technology - yTech - April 15th, 2024 [April 15th, 2024]
- Impact of aldehydes on DNA damage and aging - EurekAlert - April 15th, 2024 [April 15th, 2024]
- Redefining Cell Biology: Nondestructive Genetic Insights With Raman Spectroscopy - SciTechDaily - March 29th, 2024 [March 29th, 2024]
- Scientists Unravel the Unusual Cell Biology Behind Toxic Algal Blooms - SciTechDaily - March 19th, 2024 [March 19th, 2024]
- Ancient retroviruses played a key role in the evolution of vertebrate brains - EurekAlert - February 21st, 2024 [February 21st, 2024]
- Singapore scientists uncover a crucial link between cholesterol synthesis and cancer progression - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Scientists uncover a way to "hack" neurons' internal clocks to speed up brain cell development - News-Medical.Net - February 4th, 2024 [February 4th, 2024]
- First atomic-scale 'movie' of microtubules under construction, a key process for cell division - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Small RNAs take on the big task of helping skin wounds heal better and faster with minimal scarring - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Shengjie Feng channels the powers of cryogenic electron microscopy - Newswise - January 19th, 2024 [January 19th, 2024]
- Study pinpoints breast cancer cells-of-origi - EurekAlert - January 19th, 2024 [January 19th, 2024]
- New analysis of cancer cells identifies 370 targets for smarter, personalized treatments - News-Medical.Net - January 19th, 2024 [January 19th, 2024]
- EU funding for pioneering research on the treatment of gliomas - EurekAlert - January 19th, 2024 [January 19th, 2024]
- The future of mRNA biology and AI convergence - Drug Target Review - December 22nd, 2023 [December 22nd, 2023]
- The future of artificial breast milk, according to one lab - Quartz - December 22nd, 2023 [December 22nd, 2023]
- Shedding new light on the hidden organization of the cytoplasm - News-Medical.Net - December 22nd, 2023 [December 22nd, 2023]
- Bugs that help bugs: How environmental microbes boost fruit fly reproduction - EurekAlert - December 22nd, 2023 [December 22nd, 2023]
- Cells Move in Groups Differently Than They Do When Alone - NYU Langone Health - December 14th, 2023 [December 14th, 2023]
- Cells move in groups differently than they do when alone - EurekAlert - December 14th, 2023 [December 14th, 2023]
- Seattle Hub for Synthetic Biology plans to transform cells into tiny recording devices - GeekWire - December 14th, 2023 [December 14th, 2023]
- Virginia Tech and Weizmann Institute of Science tackle cell ... - Virginia Tech - October 16th, 2023 [October 16th, 2023]
- Vast diversity of human brain cell types revealed in trove of new ... - Spectrum - Autism Research News - October 16th, 2023 [October 16th, 2023]
- Singamaneni to develop advanced protein imaging method - The ... - Washington University in St. Louis - October 16th, 2023 [October 16th, 2023]
- Researchers find certain cancers can activate 'enhancer' in the ... - University of Toronto - October 16th, 2023 [October 16th, 2023]
- 2023 Hettleman Prizes awarded to five exceptional early-career ... - UNC Research - October 16th, 2023 [October 16th, 2023]
- Faeth Therapeutics Announces National Academy of Medicine ... - BioSpace - October 16th, 2023 [October 16th, 2023]
- From Migrant Farm Worker to Duke Scientist, Everardo Macias ... - Duke University School of Medicine - October 16th, 2023 [October 16th, 2023]
- Finding the golden ticket? Cyclin T1 is required for HIV-1 latency ... - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Spermidine May Improve Egg Health and Fertility - Lifespan.io News - October 16th, 2023 [October 16th, 2023]
- Molecule discovered that grows bigger and stronger muscles - Earth.com - October 16th, 2023 [October 16th, 2023]
- SGIOY: 3 Biotech Stocks With Potential Future Gains - StockNews.com - October 16th, 2023 [October 16th, 2023]
- Association for Molecular Pathology Publishes Best Practice ... - Technology Networks - October 16th, 2023 [October 16th, 2023]
- A new cell type with links to gastric cancer steps up for its mugshot - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Programmed cell death may be 1.8 billion year - EurekAlert - October 16th, 2023 [October 16th, 2023]
- New study confirms presence of flesh-eating and illness-causing ... - Science Daily - October 16th, 2023 [October 16th, 2023]
- New Institute for Immunologic Intervention (3i) at the Hackensack ... - Hackensack Meridian Health - October 16th, 2023 [October 16th, 2023]
- Post-doctoral Fellow in Cancer Biology in the Department of ... - Times Higher Education - October 16th, 2023 [October 16th, 2023]
- Scientists uncover key enzymes involved in bacterial pathogenicity - News-Medical.Net - October 16th, 2023 [October 16th, 2023]
- B cell response after influenza vaccine in young and older adults - EurekAlert - October 16th, 2023 [October 16th, 2023]
- Post-doctoral researcher in yeast cell biology job with UNIVERSITY ... - Times Higher Education - April 8th, 2023 [April 8th, 2023]
- expert reaction to study looking at creating embryo-like structures ... - Science Media Centre - April 8th, 2023 [April 8th, 2023]
- UCF Bone Researcher Receives National Recognition - UCF - April 8th, 2023 [April 8th, 2023]
- PhenomeX to Participate in American Association of Cancer ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Inland Empire stem-cell therapy gets $2.9 million booster - UC Riverside - April 8th, 2023 [April 8th, 2023]
- New finding in roundworms upends classical thinking about animal cell differentiation - News-Medical.Net - April 8th, 2023 [April 8th, 2023]
- Biology's unsolved chicken-or-egg problem: Where did life come from? - Big Think - April 8th, 2023 [April 8th, 2023]
- Azacitidine in Combination With Trametinib May Be Effective for ... - The ASCO Post - April 8th, 2023 [April 8th, 2023]
- Researchers clear the way for well-rounded view of cellular defects - Phys.org - April 8th, 2023 [April 8th, 2023]
- We were dancing around the lab cellular identity discovery has potential to impact cancer treatments - Newswise - April 8th, 2023 [April 8th, 2023]
- Environmental stressors' effect on gene expression explored in lecture - Environmental Factor Newsletter - April 8th, 2023 [April 8th, 2023]
- RNA therapy restores gene function in monkeys modeling ... - Spectrum - Autism Research News - April 8th, 2023 [April 8th, 2023]
- Traumatic brain injury interferes with immune system cells' recycling ... - Science Daily - April 8th, 2023 [April 8th, 2023]
- Lab-grown fat could give cultured meat real flavor and texture - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Researchers reveal mechanism of polarized cortex assembly in migrating cells - Phys.org - April 8th, 2023 [April 8th, 2023]
- Probing Selfish Centromeres Unveils an Evolutionary Arms Race - The Scientist - April 8th, 2023 [April 8th, 2023]
- Meet the 2023 Outstanding Graduating Students - UMaine News ... - University of Maine - April 8th, 2023 [April 8th, 2023]
- The Worlds Sexiest Fragrance Unveiled, But Its Not For You - Revyuh - April 8th, 2023 [April 8th, 2023]
- City of Hope appoints John D. Carpten, Ph.D., as director of its ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Modernized Algorithm Predicts Drug Targets for SARS-CoV-2, Other ... - GenomeWeb - April 8th, 2023 [April 8th, 2023]
- BU researcher wins $3.9 million NIH grant to develop novel therapeutic modalities for Alzheimer's - News-Medical.Net - April 8th, 2023 [April 8th, 2023]
- Providing critical insights for animal development - HKU biologists ... - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Students Express Frustrations About the Middle Class Scholarship - The Triton - April 8th, 2023 [April 8th, 2023]
- Mendus redeems the outstanding convertible bonds from Negma ... - GlobeNewswire - April 8th, 2023 [April 8th, 2023]
- Sustainability in research: If you want to green your lab, start with the ... - McGill Reporter - April 8th, 2023 [April 8th, 2023]
- Two-organ chip to answer fatty liver questions - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Blind dating in bacteria evolution - Newswise - April 8th, 2023 [April 8th, 2023]
- White blood cells play unexpected role in clearing out dead liver cells - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Woolly mammoths evolved smaller ears and woolier coats over the 700,000 years that they roamed the Siberian steppes - Newswise - April 8th, 2023 [April 8th, 2023]
- Pathogen mapped: Evolution and potential treatments - Science Daily - March 31st, 2023 [March 31st, 2023]
- ProJenX Announces Formation of Scientific Advisory Board - Yahoo Finance - March 31st, 2023 [March 31st, 2023]
- Science journalist Rebecca Skloot to speak on 'The Immortal Life of ... - Virginia Tech Daily - March 31st, 2023 [March 31st, 2023]
- How cell mechanics influences everything | MIT News ... - MIT News - March 31st, 2023 [March 31st, 2023]
- Artificial Cells The Powerhouse of the Future - SciTechDaily - March 31st, 2023 [March 31st, 2023]
- Basic Science Experts and Information for Media - St. Jude ... - St. Jude Children's Research Hospital - March 31st, 2023 [March 31st, 2023]
- Mendus presents an update on the use of its DCOne platform to source high-quality NK cell therapies at the 8th Annual Innate Killer Summit - Yahoo... - March 31st, 2023 [March 31st, 2023]
- Researchers reveal structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT - Phys.org - March 31st, 2023 [March 31st, 2023]
- Labroots Announces Full Agenda for its 5th Annual Bioprocessing ... - PR Web - March 31st, 2023 [March 31st, 2023]
- RoslinCT and Lykan Bioscience announce that the MHRA has granted an MIA License for their cGMP Manufacturing facilities in Edinburgh, UK - Yahoo... - March 31st, 2023 [March 31st, 2023]
- 'ASBMB opened the doors for me' - ASBMB Today - March 31st, 2023 [March 31st, 2023]