Nav: Home

New class of drugs could treat ovarian cancer

March 19, 2019

A team of researchers across The University of Manchester have shown that a new class of drugs are able to stop ovarian cancer cells growing.

The Cancer Research UK and Wellcome Trust funded study, published in the journal Cancer Cell, showed that the drugs, called PARG inhibitors, can kill ovarian cancer cells by targeting weaknesses within their ability to copy their DNA.

The first-in-class PARG inhibitor PDD00017273, was discovered in the Drug Discovery Unit at the Cancer Research UK Manchester Institute, part of The University of Manchester, as part of a targeted program to discover PARG inhibitors for the clinic.

This program is currently being progressed through a collaboration with IDEAYA Biosciences, Inc., an oncology-focused biotechnology company committed to the discovery of breakthrough synthetic lethality medicines and immuno-oncology therapies.

These findings are promising for patients diagnosed with ovarian cancer, the sixth commonest cause of cancer in women in the UK and causes more than 4,000 deaths each year.

"Sadly, for the majority of women diagnosed with ovarian cancer, the cancer relapses within 12 to 18 months of their first treatment, and so there is a pressing need to develop new therapies to treat this condition" said lead scientist Prof Stephen Taylor from The University of Manchester.

Through a collaborative effort across The University of Manchester including the Cancer Research UK Manchester Institute and The Christie , Manchester, scientists were able to screen ovarian cancer cells for specific genes that, when knocked out, would bring about PARG-inhibitor sensitivity. Through their work, the team identified the key genes that made cancer cells sensitive to PDD00017273 were those involved in DNA replication.

PhD student Nisha Pillay, provided valuable insight into how PARG inhibitors work. She said: "Before a cell divides, it must replicate its DNA. This critical process ensures the necessary amount of DNA is passed on to its daughter cells. Our research has shown that an inherent defect in the ability of an ovarian cancer cell to replicate its DNA can be exploited by the PARG inhibitor to kill the cancer cell".

"This new class of drugs is potentially very exciting and could signal a new way to help patients diagnosed with ovarian cancer in which their tumour has not responded to standard treatments".

The research team then went on to show that the PARG inhibitor can also be used in combination with other clinically accessible drugs, such as CHK1 and WEE1 inhibitors, to kill ovarian cancer cells that were taken directly from samples from patients treated at The Christie.

Dr. Robert Morgan, from The Christie, said: "We hope this work will provide further impetus for developing a PARG inhibitor for use in human trials, and also biomarkers that can be used to select the most appropriate patients to receive such treatments in the future"
-end-
NOTES FOR EDITORS

References: Pillay & Tighe et al. DNA replication vulnerabilities render ovarian cancer cells sensitive to poly (ADP-ribose) glycohydrolase inhibitors. Cancer Cell (in press)

Prof. Taylor, Nisha Pillay, Dr. Morgan are available for comment

The paper Pillay & Tighe et al. DNA replication vulnerabilities render ovarian cancer cells sensitive to poly (ADP-ribose) glycohydrolase inhibitors. Cancer Cell is available on request

This work was funded by Cancer Research UK and the Wellcome Trust.

For media enquires contact:
Mike Addelman
Media Relations Officer
Faculty of Biology, Medicine and Health
University of Manchester
0161 275 2111
07717 881567
michael.addelman@manchester.ac.uk

University of Manchester

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".