Karin Hardiman, M.D., Ph.D., the associate vice chair of basic research in the UAB Division of Gastrointestinal Surgery, and Eugenia Kharlampieva, Ph.D., professor in the UAB Department of Chemistry, have pioneered a promising new strategy to overcome one of the most persistent challenges in rectal cancer care – resistance to standard chemoradiation therapy.
Rectal cancer remains a significant clinical challenge, particularly in patients who do not respond to standard chemoradiation therapy (CRT). While CRT is a cornerstone of treatment, only a minority of patients achieve a complete response, leaving many to require major surgery and face potentially increased risks of recurrence.
Treatment resistance and novel therapies
Hardiman’s research program has previously identified a key driver of treatment resistance – the enzyme ST6GAL1, which alters cancer cell signaling and reduces apoptosis following therapy. Building on this discovery, the research team explored a novel strategy to counteract this resistance mechanism by leveraging another protein, BACE1, which can cleave ST6GAL1 and potentially restore tumor sensitivity to treatment.
“This work represents years of collaboration across surgery and chemistry to address a critical unmet need in rectal cancer,” said Hardiman. “Our goal is to develop therapies that can meaningfully improve response rates and ultimately patient outcomes.”
To translate this concept into a viable therapeutic approach, the team developed an innovative delivery system using polymersomes, which are nanoscale vesicles engineered to transport therapeutic proteins directly into cancer cells. These polymersomes encapsulate BACE1 and deliver it to tumor cells, where it acts to reduce ST6GAL1 levels and enhance the effectiveness of chemoradiation.
Preclinical findings demonstrate that this approach successfully delivers the therapeutic cargo directly to tumor cells, decreases levels of the treatment-resistance protein ST6GAL1, and significantly increases cancer cell apoptosis following chemoradiation. Importantly, the therapy showed efficacy in both cell-based models and animal models of rectal cancer - highlighting its translational potential.
Patent impact and future clinical applications
The team has filed a provisional patent through UAB's Bill L. Harbert Institute for Innovation and Entrepreneurship, marking a key step in advancing this novel technology toward clinical application.
This milestone highlights the impactful, interdisciplinary collaboration between Hardiman and Kharlampieva, whose combined expertise spans surgical oncology, cancer biology, and advanced materials science. Hardiman leads an NIH-funded laboratory focused on improving outcomes in colorectal cancer through studies of treatment resistance and metastasis. Her clinically-grounded research, shaped by her practice in colorectal and minimally invasive surgery, provides a direct pathway from discovery to patient care. Beyond her research and clinical work, Hardiman is deeply committed to investing in the next generation of surgeon-scientists. She serves as Co-Director of the Future Surgeons and Scientists Investigating Oncology (FUSSION) program and Associate Director of the Physician Scientist Development Office (PSDO). Through these roles, she mentors medical students, residents, fellows, and junior faculty, helping guide early-career investigators in both academic surgery and translational research. Her leadership in education and faculty development reflects her commitment to building a strong pipeline of future surgical leaders.
Complementing this work, Kharlampieva’s research program centers on the design of multifunctional, stimuli-responsive polymeric materials for biomedical applications, including targeted drug delivery.
With the provisional patent now filed, the research team plans to further develop and refine the therapy, with the long-term goal of clinical translation. Future efforts will focus on optimizing delivery, evaluating safety, and advancing toward early-phase clinical studies.
“This partnership has enabled us to develop a novel, nanotechnology-driven therapy that has the potential to improve patient care on a broad scale,” Hardiman said. “We are hopeful that this will one day be a new approach for patients with treatment-resistant rectal cancer.”