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Global Translational Medicine Small RNA therapy for pancreatic cancer

multiple targets, including the inhibition of tumor cell 7. Conclusion
proliferation, metastasis, and migration, disruption of the
cell cycle, induction of apoptosis, modulation of the tumor This review summarizes the current status of drug therapy
for PC and the research progress on small RNA drugs. Six
microenvironment, and enhancement of T cell-mediated strategies are proposed for developing small RNA drugs
immune responses. 112
against PC.
6. Discussion Acknowledgments

In recent years, numerous studies have provided detailed None.
insights into the extensive alterations of small RNA in
cancer. Large international cancer consortiums, such Funding
113
as The Cancer Genome Atlas and the Cancer Cell Line
114
Encyclopedia, have mapped the miRNA landscape in The study was supported by the National Natural Science
115
over 10,000 patient samples and more than 1,000 cancer cell Foundation of China (81872966), the CAMS Innovation
lines from various cancer types. These large-scale datasets Fund for Medical Sciences (CIFMS) (2021-1-I2M-022), the
have offered an unprecedented opportunity to explore the Provincial Special Project for Construction of Innovation
functional roles of miRNAs and their mechanisms of action. Demonstration Area at Chenzhou City under the National
Given the intricate nature of miRNA expression regulation, Sustainable Development Plan (2023sfq04), and the
a key challenge lies in determining whether miRNA National Science and Technology Fundamental Resources
Investigation Program of China (2018FY100705). The
dysregulation is a driving factor in disease progression or funders had no role in the study design, data collection,
merely a result of the disease development. Some miRNAs analysis, publication decision, or manuscript preparation.
function as oncogenes or tumor suppressors depending
on the tumor type, stage, and tumor microenvironment. Conflict of interest
This underscores the importance of elucidating miRNA
functions in a context-dependent manner. 116,117 The authors declare they have no competing interests.
In this review, six strategies have been proposed to develop Author contributions
small RNA drugs specifically aimed at PC. The first strategy Conceptualization: Chang Liu, Haimei Chen
is to target mRNAs involved in PC development, including Writing – original draft: Qingqing Zhou
KRAS, NF-κB, and MMP2. Furthermore, ASOs, siRNAs, Writing – review & editing: Chang Liu, Huaying Li, Guoan
and miRNA mimics can be designed to downregulate the Shen
mRNA expression of these genes. The second strategy is
to design aptamers that bind to proteins involved in PC Ethics approval and consent to participate
development and inhibit their activity. These proteins
include KRAS, NF-κB, and MMP2. The third strategy is to Not applicable.
design miRNA inhibitors to target miRNAs that promote Consent for publication
PC initiation and metastasis, thereby downregulating
their expression, such as miR-181, miR-21, and miR-155. Not applicable.
The fourth strategy is to design miRNA mimics to restore Availability of data
the expression levels of tumor-suppressive miRNAs that
inhibit PC progression, such as miR-200, miR-34, and miR- Not applicable.
143 (Table 3). The fifth strategy focuses on targeting genes
associated with chemotherapy resistance in PC. For example, References
siRNAs, ASOs, and miRNA mimics can be designed to target 1. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M.
hENT1, MRP, and DPD genes. This strategy is intended to be Pancreatic cancer. Lancet. 2011;378(9791):607-620.
used in combination with other chemotherapy drugs. Finally, doi: 10.1016/s0140-6736(10)62307-0
the sixth strategy involves targeting genes that modulate the 2. Luo YH, Luo L, Wampfler JA, et al. 5-year overall survival in
tumor microenvironment, such as P4HA1. All these targets patients with lung cancer eligible or ineligible for screening
are summarized in Tables 2 and 3. according to US PREVENTIVE SERVICES TASK FORCE
With the continuous advancement of technology, these criteria: A prospective, observational cohort study. Lancet
strategies are expected to facilitate the development of Oncol. 2019;20(8):1098-1108.
effective treatments for PC. doi: 10.1016/s1470-2045(19)30329-8

Volume 4 Issue 2 (2025) 25 doi: 10.36922/gtm.8247