Resistant pancreatic cancer found in unprecedented detail

The 5-year survival rate for pancreatic cancer is less than 11%, and the rate drops even further when the cancer metastasizes. There is an urgent need for improved treatment.Live images of drug response and tolerance ‘pockets’ now pancreatic cancer Revealed by a new tool developed by researchers at the Garvan Institute. Researchers have developed a biosensor mouse model that produces a fluorescent version of the molecule AKT found to cause cancer cell spreading, providing the first real-time view of key cancer cell signaling networks in living tissue. Offers.

The survey results are scientific progress in an article titledMonitoring AKT Activity Using Real-Time Akt-FRET Biosensor Mice and Targeting in Live Tissue and Disease Settings“

“Aberrant AKT activation occurs in many cancers, metabolic syndrome, and immune disorders, making it an important therapeutic target for many diseases,” the researchers wrote. “Akt-FRET biosensors enabling long-term assessment of AKT activity using in vivo imaging combined with image stabilization and optical window techniques to monitor spatial and temporal AKT activity in a live setting. We have demonstrated the sensitivity of Akt-FRET biosensor mice using various cancer models and validated their suitability for monitoring responses to drug targeting in spheroid and organotypic models. increase.”

“The AKT pathway has been a therapeutic target for decades, but drugs that target only this pathway have so far had little clinical efficacy,” said Cancer Ecosystem. said Dr. Paul Timpson, co-director of the Invasion and Metastasis Institute. Co-principal author of Garvan’s program and study.

A new imaging model will help researchers understand a clearer picture of how combinatorial approaches reduce drug resistance and turn off AKT to halt tumor growth and spread.

“We used intravital microscopy at the ACRF INCITe center to image biosensor models and used clinical treatments to block AKT activity, but in real-time, we found that AKT turned on within the drug resistance pocket, especially in areas close to the invasion border. Co-lead author Max Nobis, Ph.D., director of the Center of Excellence for In Vivo Imaging at the VIB-KU Leuven Center for Cancer Biology and a visiting scientist at Garvan, said: increase.

“We also found that as cancer cells approached blood vessels, AKT began to become activated. For the first time, we were able to see these events in a living pancreas.”

The researchers will then use the biosensor model to optimize novel combinations with AKT pathway inhibitors for pancreatic cancer and other AKT-driven cancers.

“The ability to detect AKT in cancer cells takes the guesswork out of developing new therapies and has broad applications as AKT contributes to many cancers, including breast and prostate cancer.” Our model is an important new tool in the era of simultaneously targeting the tumor ecosystem in precision medicine, bringing us closer to improving treatment options for patients,” said Timpson. increase.

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