(Press-News.org) LOS ANGELES — Researchers at City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the U.S. with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report, have identified a new molecular target for treating pancreatic cancer, reports a Gastroenterology study published today.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human cancers worldwide because it evades most treatments. With few therapeutic options, 90% of these patients don’t survive beyond five years. Now an innovative new approach offers the potential for transforming the genetic culprit behind PDAC’s stubborn resistance to treatment into a therapeutic ally.
Led by Mustafa Raoof, M.D., M.S., City of Hope assistant professor of surgery, cancer genetics and epigenetics, scientists focused on transcription-replication conflicts (TRCs), which occur when the mechanisms responsible for gene expression and genome duplication collide. The clash disrupts cells’ ability to read and copy genes, leading to replication stress, a frequent phenomenon in pancreatic cancer. The added stress causes cells to make errors copying their DNA, enabling cancer to gain a foothold and spread.
“Transcription-replication conflicts are an important vulnerability of pancreatic cancer,” said Dr. Raoof, senior author of the new study. “Our study is the first to confirm proof of concept for whether exploiting this chink in cancer’s armor could provide an effective therapeutic target for patients.”
In an earlier study, Dr. Raoof and his colleagues had identified high levels of TRCs as a unique weakness in pancreatic cancers that are driven by a common gene mutation. Building upon this research, his team used an experimental drug developed at City of Hope called AOH1996 as a tool to target TRCs and measure clinical responses.
First, the laboratory tested AOH1996 on a mouse model for pancreatic cancer and on small, lab-grown versions of human organs called organoids. The scientists discovered that the drug slowed tumor growth, damaged tumor cells without harming healthy tissue and boosted mouse survival from a median of 14 days to three weeks.
Next, the team tested the approach on two patients whose pancreatic tumors had resisted earlier treatments (NCT05227326). The patients experienced up to a 49% shrinkage in their liver metastases after taking the pill twice a day for two months.
Overall, the experimental approach was most effective at killing cancer cells with high replication stress, a common phenomenon that occurs when the KRAS gene goes awry in 95% of patients with pancreatic cancer.
“While the KRAS mutation has suggested a strong therapeutic target, pinpointing it in human PDAC has been difficult until now,” said Dr. Raoof. “With inhibitors to mutant KRAS entering clinical trials, resistance is expected. It’s crucial for us to develop new approaches that target dependency on KRAS.”
Targeting TRCs enabled the scientists to pinpoint only pancreatic cancer cells that experienced high levels of replication stress.
“Transcription-replication conflicts are more prevalent in cancer cells than normal cells,” Dr. Raoof said. “Therapies that interfere with how cells manage their DNA during replication could open up new ways to treat cancer, offering hope for patients who have not benefited from other approaches.”
Though excited by the study’s early results, Dr. Raoof emphasized caution in interpreting its findings. Due to the trial’s small size, scientists will need to pursue larger clinical and biomarker discovery studies to realize the full potential of therapeutic targeting of TRCs.
A respected birthplace for biotech, City of Hope created the technology that led to the development of synthetic human insulin. City of Hope later contributed to the development of “smart” cancer drugs like Herceptin, Rituxan and Avastin.
City of Hope’s Linda Malkas, Ph.D., discovered and developed AOH1996, which is exclusively licensed to the biotechnology company RLL, LLC.
Last year City of Hope received a historic $150 million gift to fund pancreatic cancer research from two entrepreneur-philanthropists: A. Emmet Stephenson Jr. and his daughter, Tessa Stephenson Brand. The donation’s mission is to accelerate leading-edge research into effective pancreatic cancer treatments through scientific partnerships with the world’s top researchers, regardless of institutional affiliation.
# # #
The Gastroenterology study entitled, “Therapeutic Targeting of Oncogene-induced Transcription-Replication Conflicts in Pancreatic Ductal Adenocarcinoma” was supported by grants from the National Comprehensive Cancer Network and the 2020 Pancreatic Cancer Action Network Career Development Award in Memory of Skip Viragh (20-20-RAOO) to the Raoof laboratory, as well as by the National Cancer Institute of the National Institutes of Health (P30CA033572) and NCCN Foundation.
About City of Hope
City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the U.S., and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked top 5 in the nation for cancer care by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.
END
When we picture sea turtles in the wild, it’s easy to envision them as armored warriors – their hard, resilient shells serving as near-impenetrable shields against oceanic threats like sharks. These sleek, streamlined shells aren’t just defensive – they’re engineered for speed, efficiency and survival. Designed to minimize drag, they allow sea turtles to glide effortlessly through the water, dive to astonishing depths, and handle the immense pressure shifts as they surface.
A sea turtle’s ...
The Korea Electrotechnology Research Institute (KERI) and the Korea Institute of Materials Science (KIMS) have jointly developed the 'spray drying technology-based high-performance dry electrode manufacturing technology' for the realization of high-capacity secondary batteries.
Secondary battery electrodes are made by mixing 'active materials' that store electrical energy, 'conductive additives' that help the flow of electricity, and 'binders' which act as a kind of adhesive. There are two methods for mixing these materials: the 'wet ...
Conventional food production and distribution systems degrade the environment due to several aspects, like overuse of fertilizers and high greenhouse gas emissions. This necessitates a shift towards low environmental impact, sustainable food systems like Community-Supported Agriculture (CSA). In CSA, consumers pay producers in advance for their harvest. In this way, farmers get financial stability, and consumers get a chance to engage in farming activities, which ultimately strengthens local food systems.
Despite its benefits, there are few studies on what makes consumers participate in CSA, particularly outside Western countries. Specifically, in Japan, where CSA ...
EMBARGOED UNTIL TUESDAY 8TH APRIL 13:25 CEST
CANNABIDIOL THERAPY COULD REDUCE SYMPTOMS IN AUTISTIC CHILDREN AND TEENAGERS
Tuesday 8th April, 13:25 CEST - New research presented at the 2025 European Congress of Psychiatry reveals that the use of cannabidiol (CBD) cannabis extract can lead to meaningful benefits and improve the behaviour of children and adolescents with autism spectrum disorder (ASD). ASD affects approximately 1 in 100 children around the world and symptoms can include difficulty interpreting language, ...
Every galaxy is thought to form at the center of a dark matter halo – a region of gravitationally bound matter that extends far beyond the visible boundaries of a galaxy. Stars are formed when gravity within dark matter halos draws in gas, but astrophysicists don’t yet know whether star-free dark matter halos exist.
Now Ethan Nadler, a computational astrophysicist at UC San Diego, has calculated the mass below which halos fail to form stars. This work was done using analytic predictions from galaxy formation theory and cosmological simulations.
"Historically, our understanding of dark matter has been ...
PROVIDENCE, R.I. [Brown University] — Just steps from the center of Tikal, a 2,400-year-old Maya city in the heart of modern-day Guatemala, a global team of researchers including scholars from Brown University have unearthed a buried altar that could unlock the secrets of a mysterious time of upheaval in the ancient world.
The altar, built around the late 300s A.D., is decorated with four painted panels of red, black and yellow depicting a person wearing a feathered headdress and flanked by shields ...
DALLAS, April 8, 2025 — For students to get their health into the endzone, a mix of various cardio and strength exercises that work different parts of the body is ideal for whole body health, according to the U.S. Department of Health and Human Services’ 2018 Physical Activity Guidelines for Americans. That is why the American Heart Association and the National Football League (NFL), in collaboration with the 32 teams, held the NFL PLAY 60 Exercise Blitz to get students moving leading up to Super Bowl LIX in New Orleans. Three schools, named the national winners of the Exercise Blitz, received $1,000 NFL PLAY 60 grants for improvements to the schools’ physical ...
A urinal designed to avoid urine splashback on the user and the floor will improve sanitation, bathroom cleanliness, and user experience.
Urinal designs have not materially changed in over a century. The style of urinal that was elevated to the status of artistic landmark by Marcel Duchamp in his 1917 dada art piece “La Fontaine” would not look out of place in today’s public restrooms. Use of a typical public urinal often results in splatter of urine outside the confines of the device—onto the floor and, most unpleasantly, onto the user, a situation that creates costly messes to clean and risks transmitting disease. Zhao Pan, Kaveeshan ...
When faced with a potential threat, mice often freeze in place. Moreover, when two animals are together, they typically freeze at the same time, matching each other’s periods of immobility.
In a new study, researchers found that coordination during fear looks different in males and females — and changes when stress is involved.
Male-female mouse pairs consistently stayed in sync during stressful situations, even when the animals were strangers. Same-sex pairs were more likely to fall out of step.
The findings, published in Biological Psychiatry Global Open Science, suggest that opposite-sex pairs may rely on a more flexible or complex coordination ...
Children with autism spectrum disorder (ASD) often experience social communication impairments and engage in restricted and repetitive behaviors (RRBs). Early identification of these symptoms is critical for timely intervention, but detecting RRBs, in particular, remains a challenge. Previous studies using eye-tracking methods have revealed that children with ASD tend to favor non-social stimuli over social ones, a preference that aligns with ASD symptoms. However, the developmental timeline of this preference—especially regarding repetitive versus random movements—remains poorly understood. Research has shown that children with ASD may spend ...
