16^th World Congress on Gastroenterology -Therapeutics & Hepatology November 21-22, 2022 London, UK

Biography:

Ran Qi has his passion in improving the treatment of pancreatic cancer. After years of clinical work experience accumulation and summary, he highlights the importance of elucidating the mechanisms of ferroptosis in chemotherapy resistance. His research provides new ideas for the improvement of chemotherapy sensitivity in cancer by blocking specific miRNA packaging into exosomes.

Abstract:

Pancreatic cancer remains one of the deadliest cancer types in the world. Severe chemotherapy resistance leads to poor prognosis in patients with advanced pancreatic cancer, highlighting the need to investigate mechanisms and develop therapies to overcome chemoresistance.

Primary NFs and CAFs were collected from PDAC patient tumor samples and paracancerous pancreatic tissues. Exosomes were isolated by ultra-centrifugation and identified via western blotting, nanoparticle tracking analysis, and transmission electron microscopy. CAF-derived miRNAs were analyzed by RT-qPCR and high‐throughput sequencing. GEM was used to induce ferroptosis, and ferroptosis levels were evaluated via measuring lipid ROS, cell viability, and intracellular Fe²⁺ levels. A xenograft tumor model was used to evaluate in vivo tumor response.

Exosomes derived from CAFs in PDAC did not exhibit innate GEM resistance. CAFs promoted chemoresistance in PDAC cells following GEM treatment by secreting exosomes, potentially through maintaining signaling communication with cancer cells. Mechanistically, miR-3173-5p derived from CAF exosomes sponged ACSL4 and inhibited ferroptosis after uptake by cancer cells.

The present study reveals a new mechanism of acquired chemo-resistance in PDAC and suggests this miR-3173-5p/ACSL4 pathway as a possible therapeutic target in Gem-resistant pancreatic cancer.