About This Project

Pancreatic cancer is one of the deadliest cancers because its cells survive by recycling their own components through autophagy. We designed a small peptide to block this process by targeting a key enzyme that activates it. To ensure delivery into tumor cells, the peptide is packaged inside exosomes, tiny natural carriers. Using pancreatic cancer cell cultures, we’ll test whether this approach can shut down autophagy and weaken tumor survival.

Ask the Scientists

What is the context of this research?

Pancreatic cancer is one of the deadliest cancers, with few treatment options and a five-year survival rate below 15%. These tumors resist therapy by relying on autophagy, a recycling process that helps them survive stress and nutrient deprivation.

Recent studies show that transcription factor EB (TFEB), a key regulator of autophagy, is activated by the enzyme calcineurin and that peptides derived from NFATc1 can bind to the same calcineurin site, preventing TFEB’s nuclear localization and activation.

Our team of high school researchers aims to test a custom NFATc1-based peptide to block this signaling pathway. To enhance its delivery and stability, we will package it inside exosomes, nanoscale natural carriers known to protect and transport therapeutic molecules

We hypothesize that delivering our calcineurin-blocking peptide via exosomes will inhibit autophagy in pancreatic cancer cells, reducing their survival and revealing a potential new therapeutic strategy.

What is the significance of this project?

Pancreatic cancer’s extreme resistance to treatment stems partly from its dependence on autophagy for survival. By directly blocking the calcineurin-TFEB pathway with our peptide, we target a specific molecular switch that drives this process. Showing that our peptide can reduce autophagy in pancreatic cancer cells would provide the first experimental evidence that this signaling step can be disrupted using a small, designed peptide.

Encapsulating the peptide inside exosomes adds a critical translational layer—demonstrating that a biologically derived carrier can safely and efficiently deliver therapeutic peptides to tumor cells. If successful, our results will validate a new precision strategy for selectively weakening pancreatic cancer’s stress-response system while minimizing harm to normal cells.

Beyond the biology, our study highlights how early-career researchers can contribute to translational cancer research by combining molecular design with innovative delivery systems.

What are the goals of the project?

This project explores whether we can block pancreatic cancer cells from using autophagy to survive. We plan to deliver a peptide called NFATc1-YLAVP, which blocks calcineurin, a key regulator of autophagy-related signaling. The peptide will be packaged in exosomes that are modified to release the peptide once inside the cells. After delivery, we will confirm cellular uptake and localization, ensuring that the peptide successfully enters cells and prevents the transcription factors from entering the nucleus.

Next, we will evaluate autophagy activity to determine whether our treatment disrupts this process in pancreatic cancer cells. Using western blot and viability assays, we’ll measure changes in key autophagy markers and overall cell survival in PANC-1 cells after treatment. By completing these experiments, we aim to determine whether our peptide-exosome system can weaken pancreatic cancer cells and open new directions for future therapies.