Each year on a Saturday in October, thousands come to the UCLA campus to be part of the L.A. Cancer Challenge, a Halloween-themed 5K walk/run benefiting pancreatic cancer research. The day brings patients, family members and supporters together to raise funds for a cause that touches thousands of lives.

The event, now in its 29th year, is hosted by the Hirshberg Foundation for Pancreatic Cancer Research, a national nonprofit dedicated to fighting the disease. Agi Hirshberg founded the organization in 1997 following the death of her husband, Ronald Hirshberg, at age 54 from the disease. Hirshberg was known as a “retail genius.” He began his career as a buyer at Filene’s, a New England department store, and rose to found and run several successful businesses. He was also a fun-loving adventurer, sailing in international competitions and riding Harley Davidson motorcycles. 

Although the pancreatic cancer survival rate is increasing, it is currently the third leading cause of cancer-related deaths in the United States. According to the American Cancer Society, in 2025, an estimated 67,440 Americans were diagnosed with this aggressive and difficult-to-detect disease, and tragically, nearly 52,000 will die from it.

Nearly 30 years ago, there were few treatment options available to Ron Hirshberg. After his death, as a gesture of gratitude for his care, his wife, Agi Hirshberg, wanted to support UCLA Health’s pancreatic cancer program. To her surprise, no such program existed at UCLA or anywhere else. Determined to find a cure, Hirshberg vowed to continue her husband’s fight against this disease.

Agi Hirshberg’s daughter, Lisa Manheim ’91 is the executive director of the Hirshberg Foundation. Manheim studied history and business at UCLA. When she graduated, she began working at the Westwood Macy’s. She says, “I was one of the youngest store managers in the company, and I loved it. I didn’t know what I wanted to be when I grew up, I just knew that I wanted to be in business.”

In 1999, Manheim was pregnant with her first child. Her mother asked if she would help with the foundation during her maternity leave. What began as a temporary arrangement turned into an indefinite stay. “We started in my mom’s living room,” Manheim recalls. “Almost 30 years later, we’ve built our foundation at UCLA. I always say there’s no better person to work for than your child’s grandmother, and the opportunity to stay connected to UCLA is a wonderful bonus.”

Manheim’s office is painted a vibrant UCLA blue. Her connection to the University is strong: all three of her sons were born at the UCLA Medical Center, and she is a season ticket holder for four different UCLA teams. “We’ve always said if somebody’s going to cure pancreatic cancer, we want it to be UCLA,” she says. “What a gift that would be!”

One of the first things Manheim and Hirshberg did was to establish the Hirshberg Foundation five pillars mission statement, a decision that has guided their work from the outset. The first pillar focuses on creating a place where patients can receive all their treatment options in one place. In 2015, the first Center opened, and in 2024 it moved into a state-of-the-art facility within the UCLA Medical Plaza to achieve this goal.

The second pillar is dedicated to funding improved patient care, enhanced treatments and increased survival rates. With the funds they raise, the foundation fuels innovation, awarding “seed grants” to institutions across the country for initial research support and “catalyst grants” for longer-term initiatives. Notably, the seed grant program has generated over $130 million in funding from the National Institutes of Health (NIH).

The third pillar is to be a resource for patients and their families. Their director of patient programs, Amy Reiss, is available to guide patients throughout their journey, from sharing resources to connecting the newly diagnosed with survivors. In addition, the Foundation funds a dedicated patient navigator at UCLA to greet patients and assist them with navigating their treatment. Manheim says, “My mom wanted to make sure that patients have somebody holding their hand, both physically and practically.”

For two decades, the Foundation has organized a patient symposium at UCLA every spring. The event evolved from presentations by doctors on their research into a collaborative forum where patients, families, doctors, caregivers and survivors share information and address questions together. The event is free of charge, entirely funded through sponsorships.

A pancreatic cancer diagnosis carries a mental toll for everyone involved. To build connection and hope, Agi Hirshberg welcomed survivors, doctors and caregivers to her home to share a meal. The event became a beloved yearly tradition known as “Casual Sunday at Agi’s.”

The fourth mission pillar is to bring people together through physical fitness to build awareness and support. Inspired by Ron Hirshberg’s love of adventure, Manheim explains, “We started the L.A. Cancer Challenge 5K because we knew Ronnie would not have wanted to go to a sit-down banquet.” The 2025 event raised more than $734,000 for cancer research.

Each year, the 5K highlights the work of an honorary medical chair — a UCLA doctor or researcher who addresses participants before the race, offering a direct connection to the work being funded by their donations. Manheim says, “I’d love to have more UCLA alumni participate. It’s a great event on a spectacular campus; I get goosebumps every time.”

The fifth pillar is to find a cure in memory of Ron Hirshberg and all pancreatic cancer patients. “The work we’ve funded has led to improved patient care, better outcomes and promising treatments on the horizon — work that would not have happened without my mom’s determination,” Manheim affirms. “Our motto is ‘never give up’ because finding a cure is worth fighting for.”

There is hope for future developments. In 2025, UCLA researchers developed a nanoparticle that carries a combination treatment with an mRNA vaccine and a small immune-boosting molecule to the liver, reprogramming it to attack pancreatic cancer. UCLA scientists are running trials on off-the-shelf cancer immunotherapies that don’t need to be custom-tailored for each patient. These treatments could ultimately be mass-produced, expanding access and reducing costs.

Thanks to the work of the Hirshberg Center, UCLA Health has become a leader in pancreatic cancer care and research. Five-year survival rates have been rising slowly, from 7% a decade ago to approximately 13% today. UCLA’s surgical oncologists perform more pancreatic surgeries than any other hospital in Southern California.

“With the progress we’ve made, we now have a community of people who are multi-year survivors. They’re the ones who are able to tell the newly diagnosed, or the people who are about to go into surgery, ‘We’ve been there. What questions do you have? You’re going to be okay.’” Manheim says, “There’s nothing like it.”

The original article appears on the UCLA Alum site, you can read the original article here.

Each year at the American Pancreas Association (APA) meeting, the conference opens with the Hirshberg Foundation Symposium. This year’s topic, pancreatic cancer cachexia, highlighted an important condition impacting many pancreatic cancer patients. Cachexia is especially common in pancreatic cancer and impacts up to 60-80% of patients. Due to this prevalence and its devastating effects on patients, cachexia is an active area of study in pancreatic cancer; researchers are aiming to uncover the mechanisms by which tumors drive this condition and discover new ways to treat these patients.

Cachexia is loss of muscle mass (muscle wasting) that cannot be reversed with food or nutrition supplementation. This muscle loss can be in combination with fat loss and decreased appetite and affects multiple organ systems leading to overall or systemic dysfunction. While anyone with an underlying disease can develop cachexia, it is commonly seen in cancer patients (25-70% of all types) and can be attributed to 20-40% of cancer-related deaths.

The Symposium began with Christopher Wolfgang MD, PhD, from NYU Langone Health and a 2006 Seed Grant Awardee, noting that, as a new faculty member 20 years ago, his first grant was from the Hirshberg Foundation. That early funding allowed his lab to establish itself and has now trained over 80 post-doctoral fellows, many of whom have stayed in academia and continue to contribute to the pancreatic cancer field. Dr. Wolfgang’s talk, Clinical Insights of Pancreatic Cancer Cachexia, introduced the clinician’s perspective on cachexia, explaining that muscle loss compounds the fact that pancreatic cancer patients are typically older and already frail. This frailty makes treatment of these patients difficult. For patients with resectable tumors, treatment is potentially curative but intense, and cachectic patients may not be able to withstand the chemotherapy/radiation and surgery combination needed to remove their tumors. Therefore, cachexia can be a huge factor limiting patient care.

A key take-away from Dr. Wolfgang’s talk is treatment options for cachexia are a vital need for the community. There are currently no approved therapies for cachexia, although there are a few showing promising results in clinical trials. More details need to be uncovered about the complex mechanisms of how tumor cells initiate the reprogramming of the body into a cachectic state and what other signals and organ systems are involved to begin to develop more therapies for cachexia. This type of research was the focus of the remaining talks of the Hirshberg Symposium as well as other sessions of the meeting.

Ashok Kumar, PhD from the University of Houston; Institute of Muscle Biology and Cachexia, spoke on Molecular and Signaling Mechanisms of Skeletal Muscle Wasting in Pancreatic Cancer Cachexia. The talk detailed his lab’s work to define cellular processes that lead to the breakdown of muscle cells. Using pre-clinical models of pancreatic cancer, Dr. Kumar’s lab discovered a pathway upregulated in muscle cells undergoing atrophy; the IRE1α-XBP1 pathway which is part of the unfolded protein response to stress in the endoplasmic reticulum (ER), where proteins are synthesized. This work suggests targeting of the IRE1α/XBP1 signaling pathway could be therapeutic for cachexia. 

Andrew Judge, PhD, from the University of Florida, also focused on the mechanisms driving muscle wasting in his talk entitled Current Updates on Cancer Cachexia Research. Dr. Judge’s lab evaluated samples from cachectic pancreatic ductal adenocarcinoma (PDAC) patients and found increased presence of immune cells, specifically macrophages and neutrophils as well as proteins involved in the complement pathway. The complement system has an important role where activation of it leads to the tagging of cells or pathogens for destruction and then clearance by the immune system. These data help define the complement signaling pathway as an important node for immune cell infiltration into muscles during cachexia and an area for more research.

The final speaker at the Hirsberg Symposium was Min Li MD, PhD, from the University of Oklahoma Health Campus. His talk, Pancreatic Cancer Cachexia: Rethink the Biology, Rebuild the Body, explained that his research found ZIP4 was increased in pancreatic cancer patients and its expression predicted cancer progression or survival. Recent work from Dr. Li’s lab has linked ZIP4 expression in pancreatic tumors to muscle wasting in preclinical models. Dr. Li’s lab found that in tumors that expressed ZIP4, zinc was increased in the cell and increased the function of zinc dependent proteins. Dr. Li’s lab found that in tumors that over-express ZIP4, zinc is accumulated in the cell and increased the function of CREB and the expression of CREB regulated genes such as RAB27A. Increased RAB27A allows for more extracellular vesicles to be released from the tumor and these EVs in turn activate p38 signaling in muscle cells turning on degradation pathways leading to muscle wasting. 

Dr. Li emphasized how the interplay between the tumor and other organ systems can control cachexia, which makes it a complex process to understand and to treat. He highlighted recent work from others in the field linking the immune system, the nervous system, and metabolic signaling to cachexia suggesting combination therapies would be necessary to address both cachexia and pancreatic cancer. 

Outside the Hirshberg Symposium, Xiling Shen, MD, from MD Anderson Cancer Center, gave a talk on Vagal Modulation of the Brain-Liver Axis to Alleviate Cancer-Associated Cachexia: Mechanistic Insights and Therapeutic Strategies.They described how dysfunction in the nervous system, specifically the vagus nerve, can affect cachexia. In preclinical models, blocking signals from the vagus nerve reversed body weight loss and increased survival, appetite, and muscle function. Dr. Shen and colleagues have developed a wearable device to temporarily and reversibly block the action of the vagus nerve using a low-frequency alternating current of electricity. This low-frequency vagal block has shown an effect on pre-clinical models and healthy volunteers for 30 hours and an initial clinical trial in pancreatic cancer patients will be starting in February of 2026 in combination with the chemotherapy cocktail FOLFIRINOX. 

From the University of Oklahoma Health Campus, Zhijun Zhou, MD’s abstract Metabolic Reprogramming Promotes Muscle Wasting and Immune Evasion in Pancreatic Cancer, was honored as one of the Hirshberg Award for Best Abstracts in Pancreatic Cancer. Dr. Zhou’s work explores cachexia as one potential reason for low response to immunotherapy typically seen in pancreatic cancer patients. Dr. Zhou’s work has found that the higher the percentage of macrophages, a type of immune cell, in the tumor correlated with the prevalence of cachexia. In preclinical models, when macrophages were depleted, the cachexia was attenuated; muscle atrophy was reduced and muscle strength was retained. Metabolic stress activates ZIP4 signaling in tumor cells which increases the expression of a protein that attracts and activates macrophages. These macrophages produce a pro-inflammatory protein that signals back to the tumor. The tumor cells then produced a protein called TWEAK that can induce cell death in muscle cells. This signaling reflects a positive feedback loop between macrophages and tumor cells that contributes to muscle atrophy and cachexia and complements the work presented by Drs. Judge, Li, and Shen. Taken together, these presentations all demonstrate the complex and interconnected pathways that drive cachexia and offer starting points for potential therapies that could combine with immunotherapy to address both cachexia and pancreatic cancer.

The talks presented throughout the APA meeting demonstrate how cachexia is an active area of study in pancreatic cancer with researchers trying to uncover the mechanisms by which this condition develops; what signals from the tumor drive the muscle wasting and the resulting multi-organ dysfunction. Cachexia in pancreatic cancer patients can limit treatment options and quality of life, so clinicians and researchers are eager to discover new ways to treat it and potentially extend patients’ lives.