Pancreatic Cancer
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Pancreatic cancer: overcoming chemotherapy resistance using synthetic anti-miRs Written by David Hackett (Ph.D. student)1, Dr. Jason McGrath (Postdoctoral Research Fellow)2, Dr. Stephen G. Maher (Associate Professor in Translational Oncology)1 Department of Surgery, Trinity St. James's Cancer Institute, Trinity Translational Medicine Institute, St. James's Hospital, D08 W9RT Dublin, Ireland. 2Department of Surgery, Royal College of Surgeons in Ireland (RCSI). 1
David Hackett
the third leading cause of cancerrelated death in the European Union.2 It has already reached this status in the United States.
Pancreatic Cancer: A Tough Nut to Crack! Pancreatic cancer presents a significant clinical challenge. Currently, the 5-year survival rate for patients diagnosed with this cancer is only 12%, the lowest among all solid malignancies.1
Pancreatic ductal adenocarcinoma (PDAC), arising in the exocrine portion of the pancreas, is the most common histological subtype of pancreatic neoplasm. It accounts for over 90% of cases of pancreatic cancer. PDAC is expected to surpass breast cancer, becoming
FEBRUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE
A multitude of factors contribute to the extremely poor prognosis of PDAC. Early-stage or localized disease is often asymptomatic. Additionally, the majority of patients present with nonspecific symptoms when the cancer is in a locally advanced or metastatic stage. As a result, only 20% of patients are eligible for curative surgery.3 Consequently, approximately 80% of patients with PDAC undergo treatment with multidrug chemotherapeutic regimens and, in some cases, radiotherapy. However, due to the aggressive tumour biology and both inherent and acquired drug resistance in PDAC cells, many patients respond poorly to current treatments.
MicroRNA Therapeutics: A Promising Anti-Cancer Treatment Approach? MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs comprising 20–25 nucleotides. They play a crucial role in gene expression regulation by imperfectly pairing with the 3′-untranslated region (3′-UTR) of target mRNA. MiRNAs have been identified as key modulators in numerous cellular processes, including those that contribute to chemotherapy resistance in various tumours.4 Therefore, miRNA-based therapy may offer a new, promising path in cancer treatment, either as a standalone option or in combination with existing standard-of-care regimens.
Figure 1 Proposed miR-31-ATOX1 Axis
