Health
City of Hope scientists develop targeted chemotherapy able to kill all solid tumors in preclinical research
The City of Hope-developed investigational small molecule selectively disrupts DNA replication and repair in cancer cells, leaving healthy cells unaffected, a new study reports.
LOS ANGELES /PRNewswire/ — Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States, today published a new study explaining how they took a protein once thought to be too challenging for targeted therapy, proliferating cell nuclear antigen (PCNA), and developed a targeted chemotherapy that appears to annihilate all solid tumors in preclinical research. As the scientists continue to investigate the foundational mechanisms that make this cancer-stopping pill work in animal models, they note that there is an ongoing Phase 1 clinical trial testing the City of Hope-developed therapeutic in humans.

Most targeted therapies focus on a single pathway, which enables wily cancer to mutate and eventually become resistant, said Linda Malkas, Ph.D., professor in City of Hope’s Department of Molecular Diagnostics and Experimental Therapeutics and the M.T. & B.A. Ahmadinia Professor in Molecular Oncology. However, the cancer-killing pill Malkas has been developing over the past two decades, AOH1996, targets a cancerous variant of PCNA, a protein that in its mutated form is critical in DNA replication and repair of all expanding tumors.
“PCNA is like a major airline terminal hub containing multiple plane gates. Data suggests PCNA is uniquely altered in cancer cells, and this fact allowed us to design a drug that targeted only the form of PCNA in cancer cells. Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out only in planes carrying cancer cells,” said Malkas, senior author of the new study published in Cell Chemical Biology today. “Results have been promising. AOH1996 can suppress tumor growth as a monotherapy or combination treatment in cell and animal models without resulting in toxicity. The investigational chemotherapeutic is currently in a Phase 1 clinical trial in humans at City of Hope.”
AOH1996 has been effective in preclinical research treating cells derived from breast, prostate, brain, ovarian, cervical, skin and lung cancers and is exclusively licensed by City of Hope to RLL, LLC, a biotechnology company that Malkas co-founded and holds financial interest in.
The researchers tested AOH1996, a small molecule PCNA inhibitor, in more than 70 cancer cell lines and several normal control cells. They found that AOH1996 selectively kills cancer cells by disrupting the normal cell reproductive cycle. It targets something called transcription replication conflicts, which occur when mechanisms responsible for gene expression and genome duplication collide. The investigational therapy prevented cells with damaged DNA from dividing in G2/M phase and from making a copy of faulty DNA in S phase. As a result, AOH1996 caused cancer cell death (apoptosis), but it did not interrupt the reproductive cycle of healthy stem cells.
“No one has ever targeted PCNA as a therapeutic because it was viewed as ‘undruggable,’ but clearly City of Hope was able to develop an investigational medicine for a challenging protein target,” said Long Gu, Ph.D., lead author of the study and an associate research professor in the Department of Molecular Diagnostics and Experimental Therapeutics at Beckman Research Institute of City of Hope. “We discovered that PCNA is one of the potential causes of increased nucleic acid replication errors in cancer cells. Now that we know the problem area and can inhibit it, we will dig deeper to understand the process to develop more personalized, targeted cancer medicines.”
Interestingly, experiments showed that the investigational pill made cancer cells more susceptible to chemical agents that cause DNA or chromosome damage, such as the chemotherapy drug cisplatin, hinting that AOH1996 could become a useful tool in combination therapies as well as for the development of new chemotherapeutics.
“City of Hope has world leaders in cancer research. They also have the infrastructure to drive translational drug discovery from the laboratory into the clinic for patients in need,” said Daniel Von Hoff, M.D., study co-author and a distinguished professor at Translational Genomics Research Institute, part of City of Hope.
City of Hope’s groundbreaking translational research history includes developing the technology underlying synthetic human insulin, a breakthrough in diabetes management, and monoclonal antibodies, which are integral to widely used, lifesaving cancer drugs, such as trastuzumab, rituximab and cetuximab.
As a next step, the researchers will look to better understand the mechanism of action to further improve the ongoing clinical trial in humans. Individuals interested in the Phase 1 clinical trial should review the eligibility requirements at clinicaltrials.gov. If eligible, call 626-218-1133 or visit City of Hope’s clinical trials webpage.
The Cell Chemical Biology study entitled “Small Molecule Targeting of Transcription-Replication Conflict for Selective Chemotherapy” was supported by the Department of Defense (W81XWH-11-1-0786, W81XWH-19-1-0326 under BC181474 and BC181474P1), National Institutes of Health/National Cancer Institute (R01 CA121289, R01 CA225843), St Baldrick’s Foundation, the Alex Lemonade Stand Foundation, Tobacco-Related Disease Research Program (TRDRP-T31IP626), Melanoma Research Foundation (MRF-717178), the ANNA Fund, RDL Foundation, Analytical Pharmacology Core supported by the National Cancer Institute of the National Institutes of Health (P30CA033572).
About City of Hope
City of Hope’s mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest 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 at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. 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 treatment facilities in Atlanta, Chicago and Phoenix. 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, Twitter, YouTube, Instagram and LinkedIn.
SOURCE City Of Hope
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Lifestyle
Finding Clinical Trial Resources

(Family Features) If you have Crohn’s disease or ulcerative colitis, a clinical trial may be an option for you. Clinical trials are necessary for finding new ways of preventing, detecting or treating these diseases and others. To learn more about inflammatory bowel disease clinical research, visit crohnscolitisfoundation.org/clinical-trials-community and consider resources from the Crohn’s & Colitis Foundation that can provide information on types of clinical trials, what to expect when participating in a clinical study, questions to ask your doctor, stories from clinical trial participants, how to find a clinical trial and more.

SOURCE:
Crohn’s & Colitis Foundation
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Lifestyle
Harness the Power of Walking: Benefits of being physically active

(Family Features) A walk isn’t just good for your body; it’s a simple, powerful way to care for your mind and soul. Physical activity, like walking, reduces stress, boosts mood and promotes overall well-being. Yet physical activity levels in the United States continue to decline, a trend threatening both mental and physical health.
Less than half of adults and fewer than 1 in 5 children in the U.S. get the recommended amount of physical activity needed for heart health, according to the American Heart Association’s 2025 Heart & Stroke Statistical Update.
National recommendations call for children to get at least one hour of physical activity each day, but the latest statistics show less than 19% of children in the U.S. achieve that target. Meanwhile, less than half of adults get the recommended 150 minutes or more of weekly physical activity.
What’s more, according to data from a National Health and Nutrition Examination Survey, 1 in 4 U.S. adults sits for longer than eight hours each day, which can have negative consequences on physical and mental health.
For decades, the American Heart Association has championed the importance of physical activity in communities across the country through events like National Walking Day on Wednesday, April 2. These tips and information can help you understand how a brisk walk can make a world of difference for heart health and mental clarity.
Benefits of Physical Activity
Staying active is one of the best ways to keep your mind and body healthy.
The physical health benefits may be obvious, but research suggests physical activity can also help bring more joy to your life. According to the 2019 Physical Activity Guidelines for Americans, people who get the recommended amount of physical activity are less likely to experience depression.
Regular physical activity enhances your mood, sharpens your mind, improves sleep and boosts overall well-being, all while reducing the risk of disease and depression and increasing both the quality and longevity of life.
How to Be More Physically Active
Exercise as simple as a brisk walk can put a major spring in your step. It can even energize you to finish other tasks at hand, whether it’s cooking or running errands. Give your daily physical activity level a boost with these tips:
- Exercising outdoors is a great way to get moving. Spending time outdoors has been shown to reduce stress, promote a sense of belonging and improve mood. It’s even better if you can enjoy the sunshine outside, which can improve mood, boost your immunity and help you get some vitamin D.
- Invite a family member or friend along with you. It’s good for them, it’s good for you and it’s good company all around.
- Instead of wondering if you’ll move today, explore how you’ll move. A walk, a dance or a stretch all count.
Getting Pets Involved
Pets are part of your family, and they can help you get healthy together. Pets provide a fun reason to spend more time outside and get the exercise needed to reduce the risk of disease later in life.
Getting moving along with your pet adds more exercise to your routine, which means living longer, reducing risk of dying from heart attack or stroke, reducing risk of diabetes, reducing stress and even boosting your overall happiness and well-being.
Exercising with your pet can also mean enjoying more socializing. You may find yourself meeting other dog owners in your area on a walk or at the dog park.
Learn more about how simple habits like walking can support your overall health at heart.org/MoveMore.
Photos courtesy of Shutterstock
SOURCE:
American Heart Association
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Food and Beverage
Add This Superfruit to Your Menu for Heart-Healthy Meals: Make recipes nutritious and delicious with avocados

(Family Features) It’s no secret that adding greens to your menu – morning, noon and night – can go a long way toward healthier eating habits. While most people think of lettuce, kale, spinach, cucumbers and Brussels sprouts, don’t forget avocados are a superfruit you can use to add good fats and great taste to recipes throughout the day.
As a versatile fruit with naturally good fats and nearly 20 vitamins and minerals, avocados have become a household staple. Avocados From Mexico is a national supporter of the American Heart Association’s Healthy for Good Initiative – Eat Smart Program, encouraging people to incorporate a variety of fruits, vegetables and other heart-healthy foods into their meals.
By supporting this initiative, Avocados From Mexico is helping to raise awareness about the importance of making smart nutrition choices. The brand’s “Good Fats Meet Great Taste” campaign, featured at select Kroger locations, highlights the importance of balanced nutrition and fresh food choices as part of an overall heart-healthy lifestyle.
Avocados provide a good source of naturally unsaturated fats, which can be part of a heart-healthy eating pattern when consumed in place of saturated fats. A well-balanced diet that includes nutrient-rich foods like avocados, whole grains, lean proteins and fiber-rich vegetables can support overall heart health. In addition to good fats, avocados are also a good source of fiber, with 3 grams per one-third of a medium avocado.
If you’re looking for an easy yet tasty way to add more avocados to your family’s menu, this Avocado, Brussels Sprout, Kale and Date Salad provides a delicious introduction to the superfruit. Loaded with greens and fit for sharing with a crowd, you can do your part to bring avocados to your nearest and dearest, neighbors or anyone you’re hosting for a fresh, better-for-you meal.
The best part: This heart-healthy dish comes together in a snap. Just process the homemade dressing featuring dates, Dijon mustard and apple cider vinegar. Then toss Brussels sprouts, kale, red onion, pistachios and, of course, avocados before combining with the dressing.
Finally, serve with shaved Parmesan cheese on the side (so guests who prefer to avoid dairy can do so) and enjoy for a fresh meal that’s equal parts delicious and nutritious. Sliced avocados are the star of the dish, with naturally good fats and nearly 20 vitamins and minerals, making this an always good, super fun recipe and a way to begin making smarter food choices.
Discover more ways to add heart-healthy meals to your menu by visiting AvocadosFromMexico.com/avocado-nutrition.

Avocado, Brussels Sprouts, Kale and Date Salad
Servings: 8
Dressing:
- 1 tablespoon lemon juice
- 2 tablespoons apple cider vinegar
- 4 dates, pitted, softened
- 2 teaspoons Dijon mustard
- 1/4 cup olive oil
- 2 Avocados From Mexico, sliced
- 6 cups Brussels sprouts, shaved or shredded
- 3 cups lacinto (dinosaur) kale, shredded
- 1 cup red onion, sliced
- 1/2 cup pistachios (or pumpkin seeds), shelled
- reduced-fat (sharp) Parmesan cheese, shaved or grated, for topping (optional)
- To make dressing: In food processor, process lemon juice, apple cider vinegar, pitted dates and mustard. Slowly add olive oil to combine.
- To make salad: In large salad bowl, combine avocados, shaved Brussels sprouts, kale, red onion and pistachios. Drizzle salad dressing evenly over greens and toss until well-coated.
- Serve with shaved Parmesan cheese, if desired.
SOURCE:
Avocados From Mexico
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