TY - JOUR

T1 - The Nexus of Inflammation-Induced Epithelial-Mesenchymal Transition and Lung Cancer Progression: A Roadmap to Pentacyclic Triterpenoid-Based Therapies

AU - Odarenko, Kirill V

AU - Zenkova, Marina A

AU - Markov, Andrey V

N1 - This research was funded by the Russian Science Foundation, grant number 19-74-30011.

PY - 2023/12

Y1 - 2023/12

N2 - Lung cancer is the leading cause of cancer-related death worldwide. Its high mortality is partly due to chronic inflammation that accompanies the disease and stimulates cancer progression. In this review, we analyzed recent studies and highlighted the role of the epithelial-mesenchymal transition (EMT) as a link between inflammation and lung cancer. In the inflammatory tumor microenvironment (iTME), fibroblasts, macrophages, granulocytes, and lymphocytes produce inflammatory mediators, some of which can induce EMT. This leads to increased invasiveness of tumor cells and self-renewal of cancer stem cells (CSCs), which are associated with metastasis and tumor recurrence, respectively. Based on published data, we propose that inflammation-induced EMT may be a potential therapeutic target for the treatment of lung cancer. This prospect is partially realized in the development of EMT inhibitors based on pentacyclic triterpenoids (PTs), described in the second part of our study. PTs reduce the metastatic potential and stemness of tumor cells, making PTs promising candidates for lung cancer therapy. We emphasize that the high diversity of molecular mechanisms underlying inflammation-induced EMT far exceeds those that have been implicated in drug development. Therefore, analysis of information on the relationship between the iTME and EMT is of great interest and may provide ideas for novel treatment approaches for lung cancer.

AB - Lung cancer is the leading cause of cancer-related death worldwide. Its high mortality is partly due to chronic inflammation that accompanies the disease and stimulates cancer progression. In this review, we analyzed recent studies and highlighted the role of the epithelial-mesenchymal transition (EMT) as a link between inflammation and lung cancer. In the inflammatory tumor microenvironment (iTME), fibroblasts, macrophages, granulocytes, and lymphocytes produce inflammatory mediators, some of which can induce EMT. This leads to increased invasiveness of tumor cells and self-renewal of cancer stem cells (CSCs), which are associated with metastasis and tumor recurrence, respectively. Based on published data, we propose that inflammation-induced EMT may be a potential therapeutic target for the treatment of lung cancer. This prospect is partially realized in the development of EMT inhibitors based on pentacyclic triterpenoids (PTs), described in the second part of our study. PTs reduce the metastatic potential and stemness of tumor cells, making PTs promising candidates for lung cancer therapy. We emphasize that the high diversity of molecular mechanisms underlying inflammation-induced EMT far exceeds those that have been implicated in drug development. Therefore, analysis of information on the relationship between the iTME and EMT is of great interest and may provide ideas for novel treatment approaches for lung cancer.

KW - Humans

KW - Lung Neoplasms/drug therapy

KW - Triterpenes/pharmacology

KW - Signal Transduction

KW - Neoplasm Recurrence, Local/pathology

KW - Epithelial-Mesenchymal Transition

KW - Inflammation/drug therapy

KW - Pentacyclic Triterpenes/therapeutic use

KW - Neoplastic Stem Cells/pathology

KW - Tumor Microenvironment

KW - aggressiveness

KW - tumor stem cells

KW - mechanism of action

KW - epithelial-to-mesenchymal transition

KW - natural products

KW - inflammation

KW - pulmonary malignancy

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85180665722&origin=inward&txGid=bd64f7ac4ffc49857fbef9ca532f3e0e

UR - https://www.mendeley.com/catalogue/9ea4fa06-ee79-3ea8-bd70-a0a49348008a/

U2 - 10.3390/ijms242417325

DO - 10.3390/ijms242417325

M3 - Review article

C2 - 38139154

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 24

M1 - 17325

ER -