PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Blocking a protein could help overcome cancer resistance to PARP inhibitors

2021-04-08
(Press-News.org) Researchers at the Francis Crick Institute have found that blocking a specific protein could increase tumour sensitivity to treatment with PARP inhibitors. Their work published in Science , suggests combining treatments could lead to improved therapy for patients with inheritable breast cancers.

Some cancers, including certain breast, ovarian and prostate tumours, are caused by a fault in the BRCA1 or BRCA2 genes, which are important for DNA repair. Treatment for these cancers has greatly improved thanks to the discovery of PARP inhibitors, drugs which capitalise on this weakness in the cancer as they block a back-up repair mechanism. This means the cancer cells cannot repair breaks in their DNA, which stops the tumour from growing.

However, in many cases, the cancer eventually develops resistance to this treatment and the tumour starts to regrow aggressively. Finding new ways to effectively kill cancer cells before this resistance develops, or re-sensitise them to treatment, is crucial to offer patients an improved chance of survival.

In their study, the research team used human cells to screen for proteins that affect their sensitivity to PARP inhibitor drugs. They found that blocking a protein, DNPH1, sensitised BRCA-defective cancer cells to treatment with the PARP inhibitor, leading to cell death in the laboratory.

Importantly, cells that had acquired resistance to the PARP inhibitor were killed when this protein was also blocked. And, as the combination did not affect healthy cells, this discovery suggests that DNPH1 is a promising target for future drug development.

Stephen West, lead author and group leader of the DNA Recombination and Repair Laboratory at the Crick says: "PARP inhibitors were a great breakthrough in the treatment of certain cancers, extending the lives of many people. However, patients have to take these drugs for the rest of their lives which sadly gives most tumours time to mutate and eventually develop resistance.

"We want to improve treatments for these patients by finding a way to strengthen PARP inhibitors so they completely kill the cancer. While more work needs to be done, in the lab and then in clinical trials, we've found a really promising potential treatment combination."

In further experiments, the researchers characterised the role of the DNPH1 protein. It acts as a 'scavenger', removing faulty nucleotides from the pool of nucleotides which are used to build DNA. Without this process, this nucleotide 'junk' is incorporated into strands of DNA. The incorporation of faulty nucleotides is the key determinant that makes the cells more susceptible to the effects of PARP inhibitors.

Kasper Fugger, lead author and postdoc in the DNA Recombination and Repair Laboratory at the Crick says: "By investigating the function of DNPH1 and finding the molecules it interacts with, we have a good understanding of how the protein works in cells. This knowledge should help us to more effectively kill cancer cells by developing an inhibitor drug, which is specific enough to be used safely in people."

The researchers are now collaborating with pharmaceutical companies to develop an inhibitor of the DNPH1 protein which, if shown to be safe and effective in clinical trials, could be used alongside PARP inhibitors as a cancer treatment.

The topic of DNA repair in cancer was the focus of a virtual conference, Medicine at the Crick, held in February. The event was part of a series which showcases major advances in biomedical science and brings together lab-based scientists together and clinicians to consider the potential impact on patient treatment.

INFORMATION:

For further information, contact: press@crick.ac.uk or +44 (0)20 3796 5252

Notes to Editors

Fugger, K. et al . (2021). Targeting the nucleotide salvage factor DNPH1 sensitizes BRCA-deficient cells to PARP inhibitors. Science . 10.1126/science.abb4542.

The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases.

An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King's College London.

The Crick was formed in 2015, and in 2016 it moved into a brand new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe.

http://crick.ac.uk/



ELSE PRESS RELEASES FROM THIS DATE:

New discovery uncovers secret switch that could revolutionise heart attack treatment

New discovery uncovers secret switch that could revolutionise heart attack treatment
2021-04-08
Scientists at the Victor Chang Cardiac Research Institute in Sydney have discovered a critical new gene that it is hoped could help human hearts repair damaged heart muscle after a heart attack. Researchers have identified a genetic switch in zebrafish that turns on cells allowing them to divide and multiply after a heart attack, resulting in the complete regeneration and healing of damaged heart muscle in these fish. It's already known that zebrafish can heal their own hearts, but how they performed this incredible feat remained unknown, until now. In research recently published in the prestigious journal, Science, the team at the Institute drilled down into a critical ...

Modern human brain originated in Africa around 1.7 million years ago

Modern human brain originated in Africa around 1.7 million years ago
2021-04-08
Modern humans are fundamentally different from our closest living relatives, the great apes: We live on the ground, walk on two legs and have much larger brains. The first populations of the genus Homo emerged in Africa about 2.5 million years ago. They already walked upright, but their brains were only about half the size of today's humans. These earliest Homo populations in Africa had primitive ape-like brains - just like their extinct ancestors, the australopithecines. So when and where did the typical human brain evolve? CT comparisons of skulls reveal modern brain structures An international ...

Novel algorithm reveals birdsong features that may be key for courtship

2021-04-08
Researchers have developed a new algorithm capable of identifying features of male zebra finch songs that may underlie the distinction between a short phrase sung during courtship, and the same phrase sung in a non-courtship context. Sarah Woolley of McGill University in Montreal, Canada, and colleagues present these findings in the open-access journal PLOS Computational Biology. Like many animals, male zebra finches adjust their vocal signals for their audience. They may sing the same sequence of syllables during courtship interactions with females as ...

Scientists discover 'jumping' genes that can protect against blood cancers

Scientists discover jumping genes that can protect against blood cancers
2021-04-08
DALLAS - April 8, 2021 - New research has uncovered a surprising role for so-called "jumping" genes that are a source of genetic mutations responsible for a number of human diseases. In the new study from Children's Medical Center Research Institute at UT Southwestern (CRI), scientists made the unexpected discovery that these DNA sequences, also known as transposons, can protect against certain blood cancers. These findings, published in Nature Genetics, led scientists to identify a new biomarker that could help predict how patients will respond to cancer therapies and find new therapeutic targets for acute myeloid leukemia (AML), the deadliest type of blood cancer in adults and children. Transposons ...

Bacteria help plants grow better

Bacteria help plants grow better
2021-04-08
Every third-grader knows that plants absorb nutrients from the soil through their roots. The fact that they also release substances into the soil is probably less well known. And this seems to make the lives of plants a lot easier. That is at least the conclusion of the current study. The participating researchers studied several maize varieties that differ significantly in their yield. In their search for the cause, they came across an enzyme, flavone synthase 2. "The high-yield inbred line 787 we studied contains large amounts of this enzyme in its roots", explains Dr. Peng Yu ...

NASA's NICER finds X-ray boosts in the Crab Pulsar's radio bursts

NASAs NICER finds X-ray boosts in the Crab Pulsars radio bursts
2021-04-08
A global science collaboration using data from NASA's Neutron star Interior Composition Explorer (NICER) telescope on the International Space Station has discovered X-ray surges accompanying radio bursts from the pulsar in the Crab Nebula. The finding shows that these bursts, called giant radio pulses, release far more energy than previously suspected. A pulsar is a type of rapidly spinning neutron star, the crushed, city-sized core of a star that exploded as a supernova. A young, isolated neutron star can spin dozens of times each second, and its whirling magnetic ...

Huntsman Cancer Institute research shows melanoma rates in Utah compared to

Huntsman Cancer Institute research shows melanoma rates in Utah compared to
2021-04-08
SALT LAKE CITY - A letter published today by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) in the New England Journal of Medicine reports that melanoma mortality among Utahns outpaced that of the rest of the United States during the period from 1975 to 2013. Melanoma death rates have been decreasing in recent years both in Utah and the United States, a trend likely attributable to new, more effective treatments, like immunotherapy. However, melanoma remains the deadliest type of skin cancer, and the incidence of melanoma diagnoses in Utahns is higher than in any other ...

New research shows that Mars did not dry up all at once

New research shows that Mars did not dry up all at once
2021-04-08
LOS ALAMOS, N.M., April 8, 2021-While attention has been focused on the Perseverance rover that landed on Mars last month, its predecessor Curiosity continues to explore the base of Mount Sharp on the red planet and is still making discoveries. Research published today in the journal Geology shows that Mars had drier and wetter eras before drying up completely about 3 billion years ago. "A primary goal of the Curiosity mission was to study the transition between the habitable environment of the past, to the dry and cold climate that Mars has now. These rock layers recorded that change in great detail," said Roger Wiens, a coauthor on the paper and scientist at Los Alamos National Laboratory, ...

Violence and its effects on healthcare service, access, and strategies

Violence and its effects on healthcare service, access, and strategies
2021-04-08
PHILADELPHIA (April 8, 2021) - Many factors, including need, affect healthcare use. Strategies geared to enhancing the provision and access to healthcare must consider the various mechanisms that contribute to healthcare need and use. Until now, the mechanism of violence and its impact on both health and healthcare use has not been investigated. A new study from the University of Pennsylvania School of Nursing (Penn Nursing) is one of the first to examine the association between violence exposure and healthcare service utilization in Mexico. Results are published in the International Journal of Health Equity. Widespread violence in Mexico can impact health through various channels. The study ...

Can a 3D printed beetle model simulate the real thing?

Can a 3D printed beetle model simulate the real thing?
2021-04-08
When it comes to choosing a partner, humans tend to be attracted by characteristics like personality and common interests. In contrast, insects tend to be a bit shallow, as they choose a mate based on appearance, and in some cases, smells. One example is the leaf beetle, which produces chemical pheromones that are on their cuticles, or the exterior surface of the beetle. They use these 'scents' to assess beetle sex and mating status (whether beetles are sexually mature or not). Kari Segraves, professor of biology in the College of Arts and Sciences, is interested in researching the chemical and visual signals that contribute to mate selection by these beetles. This work is part of a larger project focused on understanding how new species are formed. By definition, species are related ...

LAST 30 PRESS RELEASES:

Fig trees convert atmospheric CO2 to stone

Intra-arterial tenecteplase for acute stroke after successful endovascular therapy

Study reveals beneficial microbes that can sustain yields in unfertilized fields

Robotic probe quickly measures key properties of new materials

Climate change cuts milk production, even when farmers cool their cows

Frozen, but not sealed: Arctic Ocean remained open to life during ice ages

Some like it cold: Cryorhodopsins

Demystifying gut bacteria with AI

Human wellbeing on a finite planet towards 2100: new study shows humanity at a crossroads

Unlocking the hidden biodiversity of Europe’s villages

Planned hydrogen refuelling stations may lead to millions of euros in yearly losses

Planned C-sections increase the risk of certain childhood cancers

Adults who have survived childhood cancer are at increased risk of severe COVID-19

Drones reveal extreme coral mortality after bleaching

New genetic finding uncovers hidden cause of arsenic resistance in acute promyelocytic leukemia

Native habitats hold the key to the much-loved smashed avocado’s future

Using lightning to make ammonia out of thin air

Machine learning potential-driven insights into pH-dependent CO₂ reduction

Physician associates provide safe care for diagnosed patients when directly supervised by a doctor

How game-play with robots can bring out their human side

Asthma: patient expectations influence the course of the disease

UNM physician tests drug that causes nerve tissue to emit light, enabling faster, safer surgery

New study identifies EMP1 as a key driver of pancreatic cancer progression and poor prognosis

XPR1 identified as a key regulator of ovarian cancer growth through autophagy and immune evasion

Flexible, eco-friendly electronic plastic for wearable tech, sensors

Can the Large Hadron Collider snap string theory?

Stuckeman professor’s new book explores ‘socially sustainable’ architecture

Synthetic DNA nanoparticles for gene therapy

New model to find treatments for an aggressive blood cancer

Special issue of Journal of Intensive Medicine analyzes non-invasive respiratory support

[Press-News.org] Blocking a protein could help overcome cancer resistance to PARP inhibitors