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.
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.
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Kelly Kersten awarded Melanoma Research Alliance grant to support research on melanoma immunotherapy
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 theCancer 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 providesupport 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.
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,” saidLukas Chavez, PhD, associate professor in theCancer Genome and Epigenetics Programat 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, 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
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Curebound awards two grants to Sanford Burnham Prebys scientists
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.
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, 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
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, MD, Kevin Yip, PhD, and Peter Adams, PhD, with Robert James and Barbara Dudl and scholarship recipient Theo Tzaridis, MD.
The Eric Dudl Endowed Scholarship at Sanford Burnham Prebyswas 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.
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, 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, 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
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Bile may be key to immunotherapy effectiveness in liver cancer
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, is an associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.
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.”
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AI-driven cancer prediction tool makes NIH director’s highlights for 2024
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.
Most cancer deaths are caused by metastasis, but how cancer cells and tumors modify themselves and spread from their origins to other parts of the body remains largely a mystery — and fundamentally challenging.
In a new paper published December 6, 2024 in Science Advances, study co-author Sanju Sinha, PhD, assistant professor in the Cancer Molecular Therapeutics Program at Sanford Burnham Prebys, and colleagues, investigate whether primary and metastatic tumors more closely resemble the tissues of origin or target tissues in terms of gene expression.
Their findings suggest movement and evolution, providing a comprehensive transcriptome-wide view of the processes through which cancer tumors adapt to their metastatic environments before and after metastasis.
Cultured cancer cells, like these from the “immortal” HeLa human line, have proven crucial to basic cancer research. But do they accurately capture the look and behavior of living tumor cells? Kevin Tharp says no, hindering effective drug development. Image courtesy of Matthew Daniels, Wellcome Collection.
There is an art (and science) to creating cell culture models that reflect the complexities of disease. Such models have long been indispensable to parsing the underlying mechanisms of pathology and to preclinical drug discovery.
But art, writes Kevin Tharp, PhD, assistant professor in the Cancer Metabolism and Microenvironment Program, doesn’t always imitate life — at least not when it comes to finding effective cancer therapeutics.
“Just like a machine-learning algorithm trained on irrelevant datasets, efforts to discover anticancer therapeutics are limited by the models we use,” Tharp writes in the British Journal of Pharmacology. “Our drug discovery pipeline works incredibly well but is applied to models that poorly recapitulate in vivo physiology. This may be why drug discovery approaches efficiently identify drugs that work in the context tested and yet often fail to translate into clinical success.”
It’s a case of there’s no place like home. Cancer cell models are cultured on plastic in two-dimensions with limited or no diversity of neighbors. Cancer cells in vivo reside in three dimensions, with dynamic and complex interactions with neighboring cells and surroundings, i.e., the tumor microenvironment.
It’s like growing up on Disneyland’s Main Street versus a real-world urban city. Cultured cancer cells simply don’t look or behave exactly the same as cancer cells in an actual tumor. Nor do the investigational molecules being tested as potential therapies.
Tharp suggests a multi-pronged approach: Initially culture target cells using conventional methods, then transfer the cells to new culture formats that enforce distinct, non-genomic cytoskeleton architectures and expression patterns that more closed mimic real life.
