Can synthetic miR-31 mimics/anti-miRs be employed as a novel therapeutic for enhancing chemotherapy and radiotherapy sensitivity of pancreatic cancer?

David Hackett

This year the successful Musgrave PhD Scholar, in association with Breakthrough Cancer Research is David Hackett. David will work with Dr. Stephen Maher’s lab in Trinity College Dublin on pancreatic cancer. His research question is “Can synthetic miR-31 mimics/anti-miRs be employed as a novel therapeutic for enhancing chemotherapy and radiotherapy sensitivity of pancreatic cancer?”.

This proposal focuses on pancreatic cancer research, a poor prognosis cancer in Ireland and globally. Patients diagnosed with pancreatic adenocarcinoma (PDAC), which represents >90% of all pancreatic cancer cases, have an extremely poor prognosis; the vast majority of patients (~75%) will die within one year of diagnosis. PDAC has now surpassed breast cancer to become the 3rd highest cause of cancer-related death and is projected to be the 2nd most common cause of cancer-related death in the US by 2030; a trend mirrored in Europe. Less than 10% of those diagnosed with pancreatic cancer will live for 5 years after their diagnosis.

As PDAC is typically poorly responsive to chemotherapy and radiotherapy, patients achieve only modest prolongation in overall survival with these conventional therapies, frequently at a cost of significant side effects and a negative impact on quality of life. As such there is a significant need to characterise mechanisms of resistance to chemotherapy and radiotherapy in PDAC, identify predictive biomarkers to guide choice of cytotoxic therapy and develop new therapeutic approaches.

The project will investigate a promising new RNA-based therapeutic strategy to improve the effectiveness of conventional chemotherapeutic and radiotherapy regimens. The ultimate aim is to increase survival through improved treatment efficacy.

RESEARCH FINDINGS

Publications

David Hackett, Jason McGrath, Stephen G. Maher. “Pancreatic cancer: overcoming chemotherapy resistance using synthetic anti-miRs” in Hospital Professional News – Ireland (Issue 117, February, 2024) https://hospitalprofessionalnews.ie/2024/02/16/pancreatic-cancer-overcoming-chemotherapy-resistance-using-synthetic-anti-mirs/

Conference Presentations

European Association for Cancer Research Cellular Bases for Patient Response to Cancer Therapies 2023, Lyon, France. Title: “The miR-31-ATOX1 axis modulates chemosensitivity of pancreatic ductal adenocarcinoma”.

EACR-AACR-IACR Conference 2024, Dublin, Ireland. Title: “MicroRNA-31 modulates chemosensitivity via ATOX1 in pancreatic ductal adenocarcinoma”.

All-Ireland RNA Club Meeting 2024, Dublin, Ireland. Title: “MicroRNA-31 is a regulator of chemo-sensitivity in pancreatic ductal adenocarcinoma”.

39th Bennett Lecture & Upper Gastrointestinal Multidisciplinary Meeting 2024,, Dublin, Ireland. Title: “Investigating synthetic miR-31 mimics/anti-miRs as a novel therapeutic for enhancing chemotherapy and radiotherapy sensitivity of pancreatic cancer”

EACR Annual Congress 2024,  Rotterdam, Netherlands. Title “MicroRNA-31 as a novel therapeutic target to reverse chemo-resistance in pancreatic ductal adenocarcinoma”.

European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies conference 2025, Paris, France. Title “Therapeutic Inhibition of microRNA-31 to enhance Chemosensitivity in Pancreatic Ductal Adenocarcinoma”

IACR Conference 2025, Belfast, Northen Ireland. Title: “Targeting the microRNA-31-ATOX1 drug trafficking axis promotes chemosensitivity in pancreatic ductal adenocarcinoma” (Biomedical Session)

Awards

EACR-Worldwide Cancer Research Travel Grant to attend the EACR conference ‘Cellular Bases for Patient Response to Cancer Therapies’ held in Lyon, France, November 2023

IACR PhD Poster Merit Award, EACR-AACR-IACR Conference 2024, Dublin, Ireland, February 2024.

Trinity Trust Travel Grant to assist attendance at EACR 2024 Congress: Innovative Cancer Science, Rotterdam, Netherlands – Trinity College Dublin, March 2024.

Breakthrough Cancer Research Education & Travel Award 2025, European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) Congress 2025, Paris

Best Poster Award, “cellular & gene Therapies category” at the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies conference 2025

Highly Commended Display Poster Prizes, Biomedical session, IACR 2025, Belafast, Northen Ireland