Cancer Center Archives - Sanford Burnham Prebys

Tag: Cancer Center

Institute News

Preuss School interns wrap up unforgettable research experience

AuthorGreg Calhoun
Date

August 4, 2025

Preuss Intern group photo with PI mentors Image credit: Sanford Burnahm Prebys
Image credit: Sanford Burnahm Prebys

Aspiring biomedical researchers and health care professionals gained hands-on research training during three weeks at Sanford Burnham Prebys

On Friday, July 25, 2025, the Sanford Burnham Prebys community celebrated the contributions of six high school student interns from the Preuss School. Located on the University of California San Diego campus in La Jolla, the Preuss School educates students striving to be first-generation college graduates.

Participants in the Preuss internship program gained valuable hands-on research experience over three weeks. This program is generously funded by Peggy and Peter Preuss, and Debby and Wain Fishburn.

The students were split into teams of three to complete complementary experiments while studying the common fruit fly.

“The interns have learned biological concepts and experimental techniques, and also participated in career development workshops,” said Yuk-Lap (Kevin) Yip, PhD, a professor and the interim director of the Center for Data Sciences at Sanford Burnham Prebys, during the July 25 capstone presentation.

“Over the course of just three weeks, they have learned about how an unhealthy diet will affect the health of fruit flies.”

The interns discussed what attracted them to the program and presented the results of their experiments.

“I chose this program because I wanted to learn more about biology and the biomedical research field,” said intern Ahmed Ahmed.

Preuss Interns conducting experiment using fruit flies, pipetting in the lab

Image credit: Sanford Burnahm Prebys.

“I want to become a forensic scientist,” said intern Mia Gidey. “I know I need to have hands-on lab experience, so this program was really beneficial for me.” 

“This program has helped me develop a better understanding of what I would like to pursue as a career,” said intern Joshua Hernandez.

In addition to studying the effects of high-fat and high-sugar diets on fruit flies, the participant teams also had the opportunity to learn additional research techniques during workshops.

Preuss Interns conducting experiment using fruit flies, pipetting in the lab

Image credit: Sanford Burnahm Prebys.

“We were able to conduct flow cytometry experiments with our mentor, Theo Tzaridis,” said intern Bella Dinh. Flow cytometry is a technology that analyzes single cells or particles as they flow past one or more lasers while suspended in a fluid. The interns used the technique to examine proteins on the surfaces of cancer cells that affect the activity of immune cells and the effectiveness of immunotherapy.

“Our group took part in an STK4 inhibitor screening workshop with our mentor, Josh Minyard,” said intern Daniela Ledesma. The participants learned about the drug discovery and development process and went hands-on to compare the efficiency and potency of three drug candidates.

“Thank you so much to everybody that helped us throughout this journey,” said intern Kenia Avila. “We appreciate all of you and we are so grateful for everything that you’ve done.”

Katya Marchetti, a graduate student at Sanford Burnham Prebys and coordinator of the 2025 Pruess internship program, provided closing remarks following the interns’ capstone presentations.

“I am just completely blown away by how incredible every single one of you are,” said Marchetti. “Beyond the techniques and protocols you learned, I hope that you walk away from this summer with a better idea of what you might want to pursue as a career as well as the ability to think like a scientist.”

Institute News

Ani Deshpande promoted to professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys

AuthorGreg Calhoun
Date

July 16, 2025

Ani Deshpande, profile photo. Image credit: Sanford Burnham Prebys

The newly promoted scientist will continue studying how blood cancers sabotage stem cells’ special features to grow and spread

As of July 1, 2025, Ani Deshpande, PhD, was promoted to professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.

The Deshpande lab studies developmental processes in stem cells that get hijacked by cancer, focusing specifically on acute myeloid leukemia (AML), one of the most common types of blood cancer. Several attributes of normal stem cells, including the ability to self-renew, are known to be co-opted or reactivated by cancer cells.

In addition, Deshpande collaborates within and beyond the institute on several large categories of AML research, including studying the genetics of AML, studying how the disease works in animal models and working to develop drugs that can target specific mutations associated with the disease, which are numerous.

“AML has many different subtypes, so it’s been difficult for researchers to make major advances to treat all cases of AML,” said Deshpande. “Most patients with AML are given the same treatments that have been used since the 1970s, which is why we want to look at AML from as many angles as possible.”

Deshpande joined the institute in 2015 and was promoted to associate professor in 2022. Prior to arriving at Sanford Burnham Prebys, he held positions at Memorial Sloan Kettering Cancer Center and Harvard Medical School. Recently, Deshpande and colleague Pamela Itkin-Ansari, PhD, launched The Discovery Dialogues Podcast, which explores  groundbreaking discoveries in science and medicine.

“I’m deeply grateful for the incredible support of my trainees, mentors and colleagues,” said Deshpande. “And for all who made this scientific journey so meaningful and worthwhile.”

Institute News

PERCEPTION proves a predictable NCI milestone

AuthorScott LaFee
Date

May 9, 2025

false-colored scanning electron micrograph of a breast tumor spheroid
A false-colored scanning electron micrograph of a breast tumor spheroid (cluster of cells). The spheroid has been treated with the anti-cancer drug doxorubicin, which is causing some cells to die (yellow). Healthy cells are colored pink and violet. Image courtesy of Khuloud T. Al-Jamal, David McCarthy and Izzat Suffian, Wellcome Collection.

PERCEPTION is the acronym for PERsonalized Single-Cell Expression-Based Planning for Treatments In Oncology, an artificial intelligence-based tool that, in findings first reported last year, was able to predict tumor response to targeted therapy using single-cell datasets.

The work, published in Nature Cancer, is the result of first study author Sanju Sinha, PhD, assistant professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys, with senior authors Eytan Ruppin, MD, PhD, and Alejandro Schaffer, PhD, at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues.

Recently, the NCI’s Center for Cancer Research highlighted PERCEPTION in its 2024-2025 annual Milestones report.

The researchers said PERCEPTION not only helped predict which anti-cancer drugs are most effective for individual patients, but also tracked the evolution of drug resistance over the course of the disease and treatment — something never before achieved.

“A tumor is a complex and evolving beast. Using single-cell resolution can allow us to tackle both of these challenges, Sinha said when their findings were published. “PERCEPTION allows for the use of rich information within single-cell omics to understand the clonal architecture of the tumor and monitor the emergence of resistance.” (In biology, omics refers to the sum of constituents within a cell.)

“The ability to monitor the emergence of resistance is the most exciting part for me. It has the potential to allow us to adapt to the evolution of cancer cells and even modify our treatment strategy.”

PERCEPTION was previously named among the National Institutes of Health director’s highlights for 2024.

Institute News

Kelly Kersten awarded Melanoma Research Alliance grant to support research on melanoma immunotherapy

AuthorGreg Calhoun
Date

May 2, 2025

Kelly Kersten
Kelly Kersten, PhD, is an assistant professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys. Credit: Sanford Burnham Prebys

The newly created Paul Walks – MRA Young Investigator Award in Memory of Chad Johnson is part of the alliance’s $9.3 million commitment to melanoma research funding in 2025.

Kelly Kersten, PhD, an assistant professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys, was awarded a new type of grant from the Melanoma Research Alliance (MRA). The funding will support Kersten’s research on reactivating “exhausted” immune cells within melanoma tumors to restore their cancer-fighting ability and improve the effectiveness of melanoma immunotherapy.

“Inside tumors, immune cells often lose their strength to attack cancer,” said Kersten. “Our work is focused on understanding and reversing this exhaustion to make therapies more effective for more people.”

The MRA is the world’s leading nonprofit funder of melanoma research. The organization created the Paul Walks – MRA Young Investigator Award in Memory of Chad Johnson to provide support for the next generation of scientists driving innovation against melanoma.

“Our Young Investigator Awards fuel the creativity and drive of early-career scientists whose work can redefine the future of melanoma research.” said Joan Levy, PhD, MRA Chief Science Officer.

The new grant pays tribute to Chad Johnson, a beloved friend and surfer who died from his melanoma diagnosis at age 55. Funding for the award was made possible through “Paul Walks,” a community fundraiser organized by Chad’s lifelong friend, Paul Giobbi.

The Paul Walks – MRA Young Investigator Award in Memory of Chad Johnson is part of MRA’s $9.3 million commitment to fund melanoma research in 2025, supporting more than 30 researchers across the U.S., Europe and Australia. Melanoma remains the deadliest form of skin cancer, with more than 100,000 people expected to be diagnosed this year and one death every hour in the U.S. alone.

Institute News

Cancer drug finds new purpose in the brain

AuthorGreg Calhoun
Date

April 14, 2025

MRIs of responding patients throughout the course of avapritinib therapy
These representative MRIs of responding patients show tumors shrinking throughout the course of avapritinib therapy.

Scientists show that an established cancer drug travels to and shrinks some brain tumors, which may lead to new therapies for a disease with few treatments

Brain tumors are the leading cause of cancer-related death in childhood. The deadliest of these tumors are known as high-grade gliomas, with the grade referring to how quickly certain tumors grow and spread throughout the central nervous system.

Treatment options for high-grade gliomas are limited. Surgical removal is typically the first option depending on the tumor size and location. Radiation often follows to kill any remaining cancer cells to prevent another tumor from forming.

“Drug options to pair with surgery and/or radiation are few and far between,” said Lukas Chavez, PhD, associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys. “A big reason for this is the blood-brain barrier being as formidable a boundary as the mythological River Styx.”

The blood-brain barrier can, at times, mean the difference between life and death. It protects the brain and spinal cord from potential toxins and pathogens circulating in the bloodstream. However, in its vigilance, it also blocks beneficial drugs from reaching the brain. This presents a major challenge, since most medications are designed to travel through the bloodstream after being ingested or injected.

Scientists from an international team including Sanford Burnham Prebys, the University of Michigan, Dana Farber Cancer Institute, the Medical University of Vienna and many other institutions published findings March 13, 2025, in Cancer Cell demonstrating that the drug avapritinib could treat certain brain tumor cells. And, like the Styx’s ferryman Charon, the medicine is one of the rare few that can cross the blood-brain barrier known to prevent the passage of more than 98% of small molecule drugs.

The researchers selected avapritinib—which is approved by the Food and Drug Administration for treating gastrointestinal and other cancers—after finding it was the strongest commercially available drug for inhibiting the gene Platelet-derived growth factor receptor alpha (PDGFRA), which is found to be mutated in 15% of high-grade gliomas.

Lukas Chavez, PhD

Lukas Chavez, PhD, is an associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.

In addition to showing that avapritinib inhibited PDGFRA in cancer cells and mouse brain tumors, the research team tested its effects on eight human pediatric and young adult high-grade glioma patients through a compassionate-use program. The treatment was found to be safe and investigators observed that the drug caused tumors to shrink in three patients.

“More research is needed to better understand how to best repurpose this drug for high-grade gliomas,” said Chavez. “We’ll learn a lot from the ongoing Rover study, a phase 1/2 multicenter trial of avapritinib based on these findings that will include more participants.”

The authors of the new study also highlighted the need to study combining multiple targeted therapies to overcome acquired resistance to any single treatment.

Mariella G. Filbin, MD, PhD, assistant professor of Pediatrics at Harvard Medical School and research co-director of the Pediatric Neuro-Oncology Program at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, is the lead contact on the study.

Carl Koschmann, MD, ChadTough Defeat DIPG Research Professor and associate professor of Pediatric Neuro-Oncology at the University of Michigan Medical School, and Johannes Gojo, MD, PhD, head of Pediatric Precision Oncology CNS and ITCC-Lab/Clinical Trials Unit at the Medical University of Vienna, are corresponding authors along with Filbin.

Lisa Mayr, Sina Neyazi, Kallen Schwark and Maria Trissal share first authorship of the study.

Additional authors include:

  • Owen Chapman, Sunita Sridhar, Rishaan Kenkre, Aditi Dutta, Shanqing Wang, and Jessica Wang from Sanford Burnham Prebys
  • Jenna Labelle, Sebastian K. Eder, Joana G. Marques, Carlos A.O. de Biagi-Junior, Costanza Lo Cascio, Olivia Hack, Andrezza Nascimento, Cuong M. Nguyen, Sophia Castellani, Jacob S. Rozowsky, Andrew Groves, Eshini Panditharatna, Gustavo Alencastro Veiga Cruzeiro, Rebecca D. Haase, Kuscha Tabatabai, Alicia Baumgartner, Frank Dubois, Pratiti Bandopadhayay and Keith Ligon from the Dana-Farber/Boston Children’s Cancer and Blood Disorder Center and Harvard Medical School
  • Liesa Weiler-Wichtl, Sibylle Madlener, Katharina Bruckner, Daniel Senfter, Anna Lammerer, Natalia Stepien, Daniela Lotsch-Gojo, Walter Berger, Ulrike Leiss, Verena Rosenmayr, Christian Dorfer, Karin Dieckmann, Andreas Peyrl, Amedeo A. Azizi, Leonhard Mullauer, Christine Haberler and Julia Furtner from the Medical University of Vienna
  • Jack Wadden, Tiffany Adam, Seongbae Kong, Madeline Miclea, Tirth Patel, Chandan Kumar-Sinha, Arul Chinnaiyan and Rajen Mody from the University of Michigan Medical School
  • Alexander Beck from Ludwig Maximilians University Munich
  • Jeffrey Supko and Hiroaki Wakimoto from Massachusetts General Hospital
  • Armin S. Guntner from Johannes Kepler University
  • Hana Palova, Jakub Neradil, Ondrej Slaby, Petra Pokorna and Jaroslav Sterba from Masaryk University
  • Louise M. Clark, Amy Cameron and Quang-De Nguyen from the Dana-Farber Cancer Institute
  • Noah F. Greenwald and Rameen Beroukhim from the Broad Institute of MIT and Harvard
  • Christof Kramm from University Medical Center Gottingen
  • Annika Bronsema from University Medical Center Hamburg-Eppendorf
  • Simon Bailey from Great North Children’s Hospital and Newcastle University
  • Ana Guerreiro Stucklin from University Children’s Hospital Zurich
  • Sabine Mueller from the University of California San Francisco
  • Mary Skrypek from Children’s Minnesota
  • Nina Martinez from Jefferson University
  • Daniel C. Bowers from the University of Texas Southwestern Medical Center
  • David T.W. Jones, Natalie Jager from Hopp Children’s Cancer Center Heidelberg
  • Chris Jones from the Institute of Cancer Research
Institute News

Curebound awards two grants to Sanford Burnham Prebys scientists

AuthorGreg Calhoun
Date

February 12, 2025

split photo of Brooke Emerling and Michael Jackson
Brooke Emerling, PhD, is director of the Cancer Metabolism and Microenvironment Program. Michael Jackson, PhD, is senior vice president for Drug Discovery and Development in the Conrad Prebys Center for Chemical Genomics.

The San Diego-based philanthropic organization has awarded $43 million in cancer research to date

Curebound recently announced the awarding of 17 grants in December 2024 for a total of $8.25 million in funding to advance cancer research in 2024.

Two new grants will support cancer research conducted by scientists at Sanford Burnham Prebys. Since 2014, 32 Curebound grants have supported projects that included scientists at the institute.

A workaround for a tricky target

The TP53 gene contains the blueprint for constructing a protein called tumor protein p53. This protein is considered a tumor suppressor because it helps cells grow in a controlled manner.

When cell growth goes awry, however, the TP53 gene is a common culprit as the most frequently mutated gene in cancers. While this ubiquity has placed a bullseye on the mutated tumor protein p53 for aspiring drug developers, it has proven tricky to target directly.

Brooke Emerling, PhD, director of the Cancer Metabolism and Microenvironment Program, and her collaborators have shown that the growth of cancer cells with a mutated TP53 gene is dependent on lipid enzymes called phosphatidylinositol-5-phosphate 4-kinases (PI5P4K). Emerling and her collaborators have identified compounds that break down these enzymes.

The researchers have demonstrated the ability of these compounds to target and eliminate cancer cells with a mutated TP53 gene without harming normal cells. Curebound will support the team’s ongoing efforts to work around the difficult-to-target tumor protein p53 by instead targeting PI5P4K.

Next, the group plans to optimize the compounds that break down PI5P4K to develop cancer drugs that are strong candidates for future clinical trials.

Curebound collaborators: Patrick Kearney, PhD, director of Medicinal Chemistry in the Conrad Prebys Center for Chemical Genomics, and Eric Wang, PhD, assistant professor in the Cancer Molecular Therapeutics Program.

Boosting the immune system against lung cancer

The immune system is one of the main defenses of the human body to fend off harmful pathogens and invasive cells such as cancer. Among all white blood cells, a particular cell type, called a T cell, can directly kill cancer cells and therefore plays an essential role in building anti-tumor immune responses.

Immunotherapies that boost the anti-cancer capabilities of T cells have revolutionized the way we treat cancer, especially in blood cancers such as leukemia, lymphoma and myeloma. More recently, immunotherapies are rapidly advancing to become mainstream treatments for solid cancers as well.

Currently, however, less than a third of patients with lung cancer benefit from immunotherapies. Pandurangan Vijayanand, MD, PhD, the William K. Bowes Distinguished Professor at the La Jolla Institute for Immunology, discovered that certain T cells called cytotoxic T lymphocytes have molecular features associated with a robust immune response against lung cancer tumors. His work has identified new targets for lung cancer immunotherapy.

Curebound will support Vijayanand’s collaboration with Michael Jackson, PhD, senior vice president for Drug Discovery and Development in the Conrad Prebys Center for Chemical Genomics, to use this research to identify agents to boost tumor immune responses.

The research team’s work has the potential to identify a new class of immunotherapy drugs for patients with lung cancer.

Curebound collaborator: Changlu Liu, PhD, director of Receptor Pharmacology in the Conrad Prebys Center for Chemical Genomics.

Pandurangan Vijayanand

Pandurangan Vijayanand, MD, PhD, is the William K. Bowes Distinguished Professor at the La Jolla Institute for Immunology.

Institute News

Theo Tzaridis named 2024 recipient of Eric Dudl Endowed Scholarship

AuthorGreg Calhoun
Date

February 6, 2025

Theophilos Tzaridis profile photo
Theo Tzaridis, MD, a postdoctoral fellow at Sanford Burnham Prebys, was named the 2024 recipient of The Eric Dudl Endowed Scholarship.

Tzaridis, a postdoctoral fellow at Sanford Burnham Prebys, received the honor in recognition of his achievements in research on pediatric brain cancer

Theo Tzaridis, MD, was named the 2024 recipient of The Eric Dudl Endowed Scholarship at Sanford Burnham Prebys.

The scholarship fund was established at the institute to remember Eric Dudl, a postdoctoral researcher whose life was tragically cut short by cancer at the age of 33. Since 2007, 17 postdoctoral scientists have received support for their research from the endowed scholarship fund.

Tzaridis is a postdoctoral fellow in the lab of Peter Adams, PhD, director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys. He studies ways to enhance immunotherapy for diffuse intrinsic pontine glioma (DIPG), the deadliest brain tumor in children.

Tzaridis found that targeting a checkpoint molecule called CD155 leads to an enhanced immune response and tumor control. He presented the work at the annual American Association for Cancer Research conference. There he established a collaboration with a company that produces the only available antibody against CD155, enabling Tzaridis to continue his research by testing the antibody’s potential efficacy for treating DIPG in order to pave the way for a clinical trial to improve survival for patients.

David Brenner, Kevin Yip, Theo Tzaridis, the Dudls and Peter Adams

David Brenner, MD, Kevin Yip, PhD, and Peter Adams, PhD, with Robert James and Barbara Dudl and scholarship recipient Theo Tzaridis, MD.

Eric Dudl

The Eric Dudl Endowed Scholarship at Sanford Burnham Prebys was established at the institute to remember Eric, a postdoctoral researcher whose life was tragically cut short by cancer at the age of 33.

Tzaridis has garnered recognition and extramural funding throughout his career as a physician-scientist, including the 2023 Lenka Finci and Erna Viterbi Fishman Fund Award from Sanford Burnham Prebys and the best oral presentation from the American Association of Immunologists during the 2024 La Jolla Immunology Conference. His career goal is to advance research findings into clinical trials that benefit patients, including trials regarding the effective use of immunotherapy as a treatment for brain cancer.

“I’m truly grateful for the support of The Eric Dudl Endowed Scholarship,” said Tzaridis. “Eric’s inspiring legacy as an immensely dedicated postdoctoral cancer researcher lives on through the important work the scholarship helps fund.”

“Theo is an outstanding physician and a superb scientist,” said Adams. “I have no doubt that he will advance the science of brain cancer while also contributing to meaningful improvements for patients and their families.” 

For more information on setting up a scholarship or to learn more about our philanthropy program, please contact giving@sbpdiscovery.org.

Institute News

A monster, MASH

AuthorGreg Calhoun
Date

January 28, 2025

3D illustration of liver cancer
3D illustration of liver cancer.

Scientists show how the advanced form of fatty liver disease has monstrous effects on liver cancer risk

Liver cancer has proven to be a tough beast to tame. Experts expected rates of the cancer to decrease following the development of the hepatitis B vaccine in the 1980s, which reduced one of the major risk factors for the disease.

Research in Taiwan showed that its universal infant hepatitis B vaccination program led to young adults experiencing a 35.9% reduction in cases of hepatocellular carcinoma (HCC), the most common liver cancer.

Despite innovation leading to the world’s first cancer-preventing vaccine, incidence of HCC has been on the rise due to a spike in fatty liver disease over recent decades. Lifestyle factors such as high-calorie diets, excessive alcohol consumption and minimal exercise — along with genetic predispositions — can lead to problematic changes in the liver, heart and kidneys.

Specifically in the liver, growing deposits of fat in the tissue can lead over time to an advanced form of fatty liver disease marked by chronic inflammation and the accumulation of thickened scar tissue, a condition known as metabolic-associated steatohepatitis (MASH). MASH significantly increases a patient’s risk of developing HCC.

Debanjan Dhar, PhD, headshot outside

Debanjan Dhar, PhD, is an associate professor in the Cancer Genome and Epigenetics Program.

In a paper published January 1, 2025, in Nature, scientists at Sanford Burnham Prebys, the University of California San Diego, Curtin University, the University of Pennsylvania and The Liver Cancer Collaborative, demonstrated that MASH damages the DNA of liver cells. The study also linked these changes to the development of liver cancer.

Peter Adams profile photo in lab

Peter Adams, PhD, is the director of the Cancer Genome and Epigenetics Program.

“DNA damage from MASH causes liver cells to stop dividing and enter a zombie-like state called senescence,” said Debanjan Dhar, PhD, associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and coauthor on the study. “This study’s results demonstrate that some of these cells later exit senescence and are likely to become cancerous due to their accumulation of damage and mutations.”

“In the future, we can apply what we’ve learned to study potential opportunities to prevent or repair DNA damage from MASH to reduce patients’ risk of developing liver cancer,” said Peter Adams, PhD, director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and coauthor on the study.

Michael Karin, PhD, Distinguished Professor in the Department of Pharmacology at the University of California San Diego School of Medicine, is the senior and corresponding author on the study.   

Li Gu, PhD, a former postdoctoral fellow in the Karin lab, shares first authorship of the study with visiting scientist Yahui Zhu. 

Additional authors include:

  • Marcos Teneche and Souradipta Ganguly from Sanford Burnham Prebys
  • Shuvro Nandi, Maiya Lee, Kosuke Watari, Breanna Bareng, Masafumi Ohira, Yuxiao Liu, Sadatsugu Sakane, Mojgan Hosseini, Tatiana Kisseleva, Ludmil Alexandrov, Consuelo Sauceda and David Gonzalez from the University of California San Diego
  • Rodrigo Carlessi and Janina Tirnitz-Parker from Curtin Universit
  • The Liver Cancer Collaborative
  • M. Celeste Simon from the University of Pennsylvania
Institute News

Bile may be key to immunotherapy effectiveness in liver cancer

AuthorGreg Calhoun
Date

January 17, 2025

A 3D illustration of hepatocellular carcinoma
A 3D illustration of hepatocellular carcinoma, the most common liver cancer.

Understanding the crucial ingredient in bile may unlock the potential of treatments that help patients’ immune systems eliminate cancer

Hepatocellular carcinoma (HCC) is the most common liver cancer and a growing threat to public health across the globe due to the rising rate of fatty liver disease.

Liver cancer is difficult to treat as it often causes few if any symptoms early on, so it tends to be diagnosed at later, more aggressive stages. While immunotherapies that supercharge patients’ immune systems have proven effective in some cancers, this approach has had limited success in patients suffering from HCC or other forms of the disease.

Scientists are investigating the unique qualities of different tissues that may explain why the effectiveness of immunotherapy varies depending on the location of a tumor. The liver is known to have a flexible immune system capable of defending itself when necessary while not overreacting to a constant flood of foreign materials from digesting food, including metabolic byproducts from bacteria residing in the gut microbiome.

Transplant surgeons see the unique properties of the liver’s immune system firsthand when transplanted livers are typically integrated by recipients with only a low dose of immunosuppressive drugs. This ability to maintain immune tolerance, however, may reduce the ability of the liver’s immune system to find and destroy cancer cells, even when that capability is enhanced by immunotherapy.

In a paper published January 9, 2025, in Science, scientists at Sanford Burnham Prebys, the Salk Institute, the University of California San Diego, Columbia University Irving Medical Center, Memorial Sloan Kettering Cancer Center and the Geisel School of Medicine at Dartmouth, found that a critical ingredient in bile hinders the liver’s immune response against cancer.

Bile is a fluid made by the liver that assists in breaking down fats during digestion. This function is made possible by steroidal acids known as bile acids. The scientists found an increased amount of bile acids in tumor samples from patients with HCC. The team also found that genes involved in creating bile acids were being transcribed to make proteins and enzymes at an abnormally high rate in human samples and in mice genetically modified to develop liver cancer.

The authors went on to remove genes related to bile acid construction to demonstrate that mice without these blueprints developed fewer, smaller tumors. In addition, the liver’s T cells — the primary anti-tumor immune cells — were able to dig deeper into tumors and persist for longer without the immunosuppressive effects of certain bile acids.

“These findings underscore a new appreciation for the influence of bile acids on the liver’s immune system,” said Debanjan Dhar, PhD, associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and coauthor on the study. More research is needed to test the potential use of drugs to directly inhibit certain bile acids or bile acid receptors as a therapeutic strategy to reduce liver cancer growth.

Debanjan Dhar, PhD, headshot outside

Debanjan Dhar, PhD, is an associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.

Peter Adams profile photo in lab

Peter Adams, PhD, is the director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.

It may also be possible to achieve this effect through dietary changes that alter the microbiome and result in modified bile acid production. Based on their findings, the research team suggests that this could be done by using ursodeoxycholic acid, a bile acid that currently is used to treat an autoimmune condition called primary biliary cholangitis. The acid is found at high levels in bear bile, which has served for thousands of years as a treatment in traditional Chinese medicine.

“Given the safety profile of ursodeoxycholic acid and the limited effectiveness of immunotherapy on liver cancer, this study shows significant potential for testing this bile acid as a combination treatment for patients with HCC,” said Peter Adams, PhD, director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and coauthor on the study.

Susan Kaech, PhD, NOMIS Chair, professor and director of the NOMIS Center for Immunobiology and Microbial Pathogenesis at the Salk Institute is the senior and corresponding author on the study.   

Siva Karthik Varanasi, PhD, assistant professor at the UMass Chan Medical School and a former postdoctoral fellow in the Kaech lab at the Salk Institute, is first author on the manuscript. 

Additional authors include:

  • Souradipta Ganguly, Marcos G. Teneche and Aaron Havas, from Sanford Burnham Prebys
  • Dan Chen, Melissa A. Johnson, Kathryn Lande, Michael A. LaPorta, Filipe Araujo Hoffmann, Thomas H. Mann, Eduardo Casillas, Kailash C. Mangalhara, Varsha Mathew, Ming Sun, Yagmur Farsakoglu, Timothy Chen, Bianca Parisi, Shaunak Deota, H. Kay Chung, Satchidananda Panda, April E. Williams and Gerald S. Shadel, from the Salk Institute
  • Yingluo Liu, Cayla M. Miller, Jin Lee and Gen-Sheng Feng, from the University of California San Diego
  • Isaac J. Jensen and Donna L. Farber, from Columbia University Irving Medical Center
  • Andrea Schietinger from Memorial Sloan Kettering Cancer Center
  • Mark S. Sundrud from the Geisel School of Medicine at Dartmouth

Wolfram Goessling, MD, PhD, the Robert H. Ebert Associate Professor of Medicine and associate professor of Health Sciences and Technology at Harvard Medical School, authored a Perspective article on the new study in Science called, “Ena-bile-ing liver cancer growth.”

Institute News

AI-driven cancer prediction tool makes NIH director’s highlights for 2024

AuthorScott LaFee
Date

January 3, 2025

illustration of AI driven data

On April 18, 2024, first author Sanju Sinha, PhD, an assistant professor in the Cancer Molecular Therapeutics Program at Sanford Burnham Prebys, and colleagues published details about a new artificial intelligence-powered tool called PERCEPTION (PERsonalized Single-Cell Expression-Based Planning for Treatments In ONcology).

PERCEPTION was proof-of-concept that AI could be used to predict a cancer’s treatment responses from bulk RNA. Sinha and colleagues built AI models for 44 drugs approved by the FDA and found that their tool “predicted the success of targeted treatments against cell lines with a high degree of accuracy.”

The paper was among six specifically highlighted by Monica Bertagnolli, MD, in her blog as director of the National Institutes of Health.