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Gene & Protein in Disease MOR in cancer

inhibits the release of excitatory neurotransmitters and MOR3 as well as inhibit cancer cell proliferation at
from the presynaptic membrane and the postsynaptic high concentrations. However, there are studies that have
membrane depolarization, both of which are attenuated revealed contradicting results, such as a study of renal cell
by PD-1 inhibition [111] . Therefore, further exploration carcinoma demonstrating that morphine has little effect
of the interaction between PD-1 and MOR is needed to on tumor proliferation at low concentrations but has
modify the immunotherapy regimen and develop new significant proliferative effect at high concentrations [117] .
immunotherapies for different types of cancer. These results indicate that MOR drug concentration
To date, the effect of morphine on cancer progression variations produce noticeable outcomes that are closely
has been extensively studied. However, recent studies have related to cancer types and gene expression, and the related
suggested that exogenous opioids can also regulate the effect can be blocked by MOR inhibitors. These findings
proliferation of cancer cells by binding to opioid growth have revealed the potential of MOR as a new target in
factor receptor (OGFR) [114,115] . OGFR differs from classical cancer treatment. However, the molecular mechanism of
opioid receptors in that it does not have any analgesic effect such possible influencing factors is unclear, and there is a
and is a negative regulator of cell proliferation. Research lack of relevant case records in clinical practice. Therefore,
findings have shown that lung cancer cells express OGFR there is a need to design more prospective studies to
and morphine might inhibit the progression of lung cancer determine the relationship between the overall survival
by interacting with OGFR [116] . On this basis, we speculate rate of cancer patients and opioid use (such as duration
that a combination therapy targeting MOR and OGFR may of administration and drug concentration), the level of
be beneficial for inhibiting cancer progression. In short, MOR expression in different cancer cells, and the changes
immunotherapy for cancer treatment is of great research in MOR expression in different cancer processes. Through
value, and further research on MOR may provide new clinical epiphenomena, we can steer the research direction
ideas for cancer treatment. of molecular mechanism and understand the role of MOR
in inhibiting cancer development, thus blocking its path of
4. Conclusion and perspective promoting tumorigenesis and tumor development as well
Recent investigation has demonstrated that high MOR as improving the prognosis of cancer patients.
expression could promote the proliferation of cancer cells In conclusion, based on the previous research results, we
by activating AKT/mTOR, cAMP/PKA, and MAPK- anticipate the possibility of further exploring the interactions
related signaling pathways, which would directly lead among MOR, PD-1, OGFR, etc., and using these relationships
to poor prognosis in LSCC patients, shortened PFS and to study new immunotherapies for cancer treatment and
OS in patients with metastatic PC, proliferation of PC provide novel ideas for the treatment of tumors.
cells, and increased chemotherapy resistance. However,
downregulating the expression of MOR could inhibit the Acknowledgments
progression of human liver cancer. On the other hand, None.
MOR activation could inhibit angiogenesis and tumor
development in LCC by inhibiting the HIF-1α/p38 MAPK Funding
pathway. These findings partially indicate that there may be
a “dual action” relationship between opioids and the MOR This work was supported by the Program for Innovative
on which opioids mainly act and the development of cancer. Talents of Science and Technology in Henan Province
Therefore, further exploration of the specific mechanism (No. 23HASTIT043), the Natural Science Foundation
and inhibition of the signaling pathway that can promote of Henan Province for Excellent Young Scholars
tumorigenesis and development are the research directions (No. 212300410026), the Medical Science and Technology
on the impact of tumor duality using MOR. Program of Henan Province (No. SBGJ202103096), and
the Program for Young Key Teacher of Henan Province
Several factors, including cancer type, cancer process, (No. 2020GGJS037).
time of drug administration, drug concentration, and drug
administration route, have more or less influence on the role Conflict of interest
of opioids in the development of cancer. A large number
of studies have demonstrated some controversial results The authors declare no conflict of interest.
due to the use of opioids at different concentration levels, Author contributions
thus activating different subtypes of MOR and resulting in
the dual effect on cancer progression and prognosis. MOR Conceptualization: Shuangyu Lv, Xinying Ji
agonists have shown to promote the development of cancer Writing – original draft: Ruidong Ding, Yiming Zhao, Jia
cells at therapeutic concentrations by activating MOR1 Li, Siyuan Zhao

Volume 2 Issue 2 (2023) 12 https://doi.org/10.36922/gpd.282