Pancreatic cancer is one of the most difficult cancers to treat. Researchers at MUSC Hollings Cancer Center believe a genetic mutation may offer important clues, revealing vulnerabilities that could improve emerging cancer treatments.
A new grant from the Pancreatic Cancer Action Network (PanCAN), a national nonprofit dedicated to advancing pancreatic cancer research and patient support, is helping Hollings researcher Aaron Hobbs, Ph.D., to pursue that possibility. Hobbs received a 2026 PanCAN Research Recovery Grant, a one-year award designed to aid investigators in maintaining research momentum when external funding delays threaten to slow promising projects.
By studying how this unusual oncogenic mutation shapes pancreatic tumor biology, Hobbs and his team hope to uncover hidden weaknesses in cancer cells – insights that could guide the development of more effective therapies.
“These awards help us make forward progress,” Hobbs said. “We’re asking questions that could directly influence how therapies are developed and how patients are treated. Once we understand how pancreatic cancer survives, we can identify new ways to treat it.”
Unlocking one of pancreatic cancer’s biggest drivers
At the center of Hobbs’ project is KRAS, a gene described as the engine of pancreatic cancer. KRAS mutations are common in many cancers but especially so in pancreatic cancer.
More than 90% of pancreatic cancers contain mutations in KRAS, which acts as a master switch that tells cells to grow and survive. When the gene mutates, that switch can become stuck in the “on” position, causing cells to grow uncontrollably.
Although researchers have spent decades trying to target KRAS, effective therapies have only recently begun to emerge. Many questions remain about how KRAS functions in cancer.
“When we inhibit KRAS, tumors often find ways around it,” Hobbs said. “Understanding those escape routes is essential if we want these therapies to work more effectively.”
Hobbs’ research will focus on a particularly unusual version of the gene, known as KRAS G12R, found almost exclusively in pancreatic tumors. Because G12R behaves differently from other KRAS mutations, it may reveal new weaknesses to target in pancreatic cancer.
Identifying a hidden survival pathway in pancreatic tumors
Cancer cells rely on networks of signaling pathways that control how they grow and survive.
The two main pathways by which KRAS mutations drive pancreatic cancer are MAPK, which promotes cell growth, and PI3K, which helps cancer cells to survive under stress. The assumption has been that KRAS G12R activates both pathways.
We’re making real progress. Discoveries are happening in the background right now, and they’re going to translate into better treatments.
However, Hobbs’ earlier research uncovered something unexpected.
The KRAS G12R mutation cannot activate the PI3K pathway in the usual way. Yet pancreatic tumors carrying this mutation still develop.
“That raised a big question,” he said. “If this mutation doesn’t activate one of cancer’s key survival pathways directly, then how is the tumor still growing? If you inhibit KRAS, but the pathway is still active, the tumor will continue to persist.”
The answer appears to be that pancreatic cancer cells can activate the PI3K pathway through other mechanisms – independent of KRAS. That discovery could explain why some therapies targeting KRAS alone may not be enough to stop pancreatic cancer.
Understanding how pancreatic cancer activates this pathway and how to block it safely could help Hobbs and other researchers to design combination therapies that make new KRAS inhibitors more effective.
Building better models to test pancreatic cancer therapies
Another goal of the project is to improve how pancreatic cancer is studied in the lab.
Hobbs’ team previously developed a specialized mouse model carrying the KRAS G12R mutation. Surprisingly, mice did not develop pancreatic cancer – reinforcing the idea that additional biological mechanisms must be causing the cancer to form in humans.
With support from the PanCAN grant, the researchers now hope to refine the model so that it better reflects how pancreatic cancer develops and behaves in human patients.
According to Hobbs, animal models remain an essential step between discoveries in the lab and clinical trials in humans.
“These models allow us to study cancer within a whole organism – with an immune system, metabolism and all the complexities of living biology,” Hobbs explained. “Those factors are difficult to replicate in cell culture studies alone.”
By creating models that more closely mirror human disease, researchers can better evaluate potential therapies and identify treatments that are more likely to succeed.
Keeping progress moving forward
Although pancreatic cancer remains difficult to treat, Hobbs said the field may be approaching a turning point.
Researchers now have a deeper understanding of the disease’s biology, and new targeted therapies are emerging. The next challenge is figuring out how to make those treatments work better and last longer for patients.
“We’re making real progress,” Hobbs said. “Discoveries are happening in the background right now, and they’re going to translate into better treatments.”
He believes investments made in pancreatic cancer research over the past decade could soon begin to shift survival rates, with the potential for meaningful improvements over the next five years.
Sustaining that progress will be critical to turning today’s discoveries into tomorrow’s treatments. Programs like PanCAN’s Research Recovery Grant support researchers during times when the funding climate for biomedical research is challenging. This allows labs like Hobbs’ to keep generating critical data while pursuing larger federal grants. For Hobbs, that includes a major research grant submitted to the National Institutes of Health.
“These funds help sustain my research program and keep our team moving forward,” he said. “If we maintain this momentum, I believe we’re very close to making a real difference for patients.”
Hollings researchers, clinicians, patients and supporters will take part in PanCAN’s upcoming PurpleStride event in Charleston as part of the Wage Hope With Hollings team, raising funds that directly support pancreatic cancer research at Hollings.
Community events like these connect the Hollings research community with patients and families across South Carolina, underscoring the direct impact of ongoing work at MUSC. By participating, the Hollings team also helps to ensure that national fundraising efforts translate into local progress, advancing research and care for patients in South Carolina.
Hobbs said events like PurpleStride are a powerful reminder of why the work matters.
“It’s incredibly meaningful to see the pancreatic cancer community come together for a common goal,” he said. “It reminds us that the research we’re doing in the lab is directly connected to people who are counting on progress.”
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Aaron Hobbs, Ph.D.
RAS family small GTPases have been my top research interest since I began graduate school. Constitutively active RAS family GTPases are involved in numerous cancers, and RAS has been considered “undruggable” for decades. While the “undruggable” veneer has finally been shattered, developing effective RAS-targeted therapies remain a top priority in the cancer field. My studies on RAS can be grouped into two themes. First, I have extensive experience examining the role of thiol oxidation on modifying the biochemical properties and signaling of KRAS and RAS superfamily GTPases. Second, utilizing KRASG12R as a model, I demonstrated that all RAS mutations are not created equal. KRASG12R is present in approximately 15% of pancreas cancer patients yet is rare in other cancers. Pancreatic cancer has a low five-year overall survival rate of 11%, which highlights a clear need for effective therapeutic strategies. My research contributions describing mutation-specific signaling have shifted the paradigm in the RAS field, definitively showing a role for mutant-specific effector signaling and highlights my overall research objective, developing mutation-selective therapies for RAS-mutant cancers.
Hayley Kamin
Communications Manager
Hayley Kamin is the communications manager for the Hollings Cancer Center Communications and Marketing team, having joined the team in 2025 after three years as a communications specialist at the National Institutes of Health (NIH). As a science communicator with a Ph.D. from the University of Florida, she has extensive experience translating complex research into clear, engaging content. Her career has included roles at the NIH’s National Institute of Mental Health and the American Psychological Association, where she led content development and editorial strategy, developed science and health communications and worked with researchers and clinicians to strengthen public understanding of research.
