From the Bench, Spring 2025: Making Tumors Pig-like, Transplanting Fat Cells, and Other Creative Approaches in Cancer Research

In this edition of From the Bench, researchers take bold steps to reimagine what cancer treatment and detection could look like. What if you could trick the immune system into seeing tumors as pig organs so they are rejected? Or design a synthetic receptor with remote control settings? One team even asked: Could fat cells—yes, fat cells—starve tumors into submission? 

This season’s roundup also includes a cleverly named blood test for pancreatic cancer that may help catch the disease in its earliest stages, as well as a large-scale study that pieces together how prostate tumors evolve, with an eye toward more precise early diagnostic strategies. 

Together, these inventive approaches highlight the creativity and cross-disciplinary thinking fueling today’s cancer research and hint at where the field is headed next. 

Unleashing Circe: Turning Tumors Pig-like to Trigger Antitumor Immunity in Patients

In Homer’s “Odyssey,” the sorceress Circe famously turned Odysseus’ crew into pigs. In a new study, cancer researchers are taking a similar approach to combat cancer—making tumors pig-like.

Organ rejection is a common issue facing transplant recipients, particularly when patients receive organs from pigs. This occurs because a patient’s immune system recognizes the transplanted organ as foreign and mounts an attack against it. In an article published in Cell, researchers from Guangxi Medical University and other institutions in China reported how they could exploit the mechanisms underlying pig organ rejection to devise a new strategy to fight tumors.

The researchers designed an oncolytic virus that expresses alpha 1,3-galactotransferase (α 1,3-GT), which is the protein in pig organs that triggers the human immune system to attack the organs after transplantation. Since the oncolytic virus preferentially replicates in cancer cells, the approach ensures that α 1,3-GT is expressed primarily by cancer cells and that the subsequent immune response is targeted to cancers and not healthy tissue—in essence, making human tumors resemble pig organs so that the immune system attacks them.

The strategy was effective in cynomolgus monkeys with liver cancer, inducing an immune response and extending survival by several months. In a clinical trial, the oncolytic virus led to disease control in 18 of 20 patients with treatment-refractory cancers, including one complete response and six partial responses. The authors suggest that these preliminary results support the strategy’s efficacy and potential for clinical translation.

Back to the ’90s: Transmitting Messages Through PAGERs

It’s 2025, but a new study out of Stanford University, published in Nature, suggests that PAGERs might still be relevant. In this case, researchers are referring to a new cell signaling system they developed, which they call “programmable antigen-gated G-protein-coupled engineered receptors” (PAGERs).

PAGERs are synthetic receptors designed to activate a signaling pathway of choice upon binding to an extracellular target antigen. Like prior synthetic receptor approaches, PAGERs allow researchers to reprogram cell behavior for cancer research and treatment. Unlike prior synthetic receptor approaches, however, PAGERs can pair with mobile antigens (no pun intended!) and have built-in drug control.

The PAGER design includes an autoinhibitory nanobody domain that binds to the receptor and keeps it “off” unless the target antigen is present. In the presence of the target antigen, the autoinhibitory domain releases from the receptor in order to bind to the antigen, and the receptor becomes available to bind to an activating drug, which triggers activation of downstream signaling. This two-step system ensures that downstream signaling is activated only when the target antigen and activating drug are both present.

The researchers demonstrated potential applications of the system, such as promoting T-cell migration in response to a soluble antigen, controlling when macrophages differentiate, and secreting antitumor antibodies upon detection of a tumor antigen.

Hungry, Hungry Lipo(cytes): Outcompeting Cancers for Essential Nutrients

Cancers are characterized by a voracious “appetite”—a heightened ability to consume and metabolize nutrients to fuel their growth. But what if you surround cancer cells with cells with an even bigger appetite?

In a recent study published in Nature Biotechnology, researchers from the University of California San Francisco and other institutions demonstrated that they could essentially starve cancers by transplanting fat cells (also called “lipocytes” or “adipocytes”) that are engineered to outcompete cancer cells for essential nutrients.

The fat cells were engineered to have higher-than-normal expression of the UCP1, PRDM16, or PPARGC1A genes, which led to increased glucose and fat metabolism. When these engineered fat cells were cocultured with cancer cell lines, the cancer cells exhibited significantly reduced proliferation and decreased glucose uptake and metabolism. Similarly, transplanting the engineered fat cells into mice reduced tumor size and suppressed cancer progression. The authors propose their strategy as a potential therapeutic approach for a variety of cancer types.

One Stop Washout: A Three (target)-in-One CAR T-cell Conditioner for Leukemia 

Acute myeloid leukemia (AML) is a deadly disease that’s difficult to treat and even harder to keep in remission, especially in children. Standard therapy involves aggressive chemotherapy to clear out the diseased bone marrow, followed by a stem cell transplant to provide healthy new hematopoietic stem cells. But this approach comes with harsh, often serious side effects. Worse, some leukemias come roaring back even after this grueling process, fueled by stubborn leukemia stem cells that resist standard treatment. 

As highlighted in a study published in Molecular Therapy: Oncology, scientists from the Stanford University School of Medicine and University of Wisconsin-Madison have engineered a new kind of CAR T-cell therapy, cleverly dubbed “ELECTRIC CARs,” to address these exact problems. These genetically modified immune cells are designed to recognize and attack three targets—KIT, FLT3, and MPL—all at once. Importantly, these targets are expressed by both normal blood cells and leukemia cells within the bone marrow, so the CAR T cells eliminate cancer cells while also clearing out the microenvironment. This helps prep the bone marrow for a new stem cell transplant, without the need for traditional chemotherapy. 

In lab tests and mouse xenograft models, ELECTRIC CARs showed impressive potency against AML. If proven safe and effective in humans, these novel CAR T cells could radically transform AML care, offering a less toxic way to fight a notoriously tough cancer while setting the stage for lasting recovery. 

PAC-MANN: A Game-Changer in Pancreatic Cancer Detection 

Pancreatic cancer is notoriously difficult to detect early, often leading to poor survival rates. While CA 19-9 represents the gold standard blood-based biomarker for pancreatic cancer, it does not catch all cases, so incorporating other molecules linked to disease could enable earlier detection and hopefully better outcomes for patients. 

To that end, a team from Oregon Health & Science University and Stanford University School of Medicine developed PAC-MANN, a new blood test that uses a tiny blood sample to detect the activity of enzymes that remodel the pancreatic tumor environment, and published their work in Science Translational Medicine. PAC-MANN could distinguish between pancreatic ductal adenocarcinoma (PDAC) and healthy tissue as well as noncancerous pancreatic disease. Furthermore, combining PAC-MANN with CA 19-9 analysis enabled the detection of stage 1 PDAC with high sensitivity and specificity. Beyond detection, PAC-MANN may also help monitor treatment effectiveness by tracking changes in protease activity over time, as one study showed. 

As this technology is refined and validated, PAC-MANN could become a powerful tool that enables earlier detection of pancreatic cancer, with a simple blood draw, and provide doctors a better opportunity to cure patients. For a disease that often hides until it’s too late, this could help flip the script and bring pancreatic cancer out of the shadows. 

Profiling Progression in Pseudotime: Mapping the March of Prostate Cancer 

A prostate tumor isn’t a single, unified enemy. It’s a swarm of cancer cells, each mutating at its own pace and marching along its own evolutionary path. This can result in a cellular mosaic where some regions are still relatively benign, while others are advancing toward aggressive disease. This diversity within a single tumor makes it incredibly difficult to assess how aggressive the cancer really is, especially in its early stages. That complexity has long stood in the way of developing reliable diagnostic tools that can detect high-risk prostate cancer before it progresses. 

To address this challenge, researchers at Xuzhou Medical University in China, the Karolinska Institutet in Sweden, and other institutions, published a new study in the AACR journal Cancer Research in which they analyzed tumors from more than 2,000 prostate cancer patients across three major datasets. They used spatial transcriptomics to map which genes are active within different regions of the tumor, “pseudotime” analysis to reconstruct the stepwise evolution of cancer cells, and machine learning to uncover consistent patterns of progression across samples. By tracing how different regions of the tumor diverge along distinct molecular paths, the team aimed to capture the hidden dynamics that shape how prostate cancer unfolds. Ultimately, stitching all of this information together enabled the researchers to build a dynamic model of prostate tumor progression.

Crucially, they also determined that biomarkers related to some of these molecular signals could be detected in blood and urine, offering a potential path toward noninvasive diagnostics that reflect the tumor’s internal complexity, and one that could help clinicians detect aggressive prostate cancers earlier and more precisely. Rather than relying on static snapshots, this study offers a roadmap of how prostate cancer evolves over time and space, potentially transforming how we diagnose and treat the disease before it takes a dangerous turn.