Articles

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Glaviano, Antonino; Lau, Hannah S.; Carter, Lukas M.; Lee, E. H. C.; Lam, Hiu Y.; Okina, Elena; Tan, Donavan J. J.; Tan, Wency; Ang, Hui L.; Carbone, Daniela; Yee, Michelle Y.; Shanmugam, Muthu K.; Huang, Xiao Z.; Sethi, Gautam; Tan, Tuan Z.; Lim, Lina H. K.; Huang, Ruby Y.; Ungefroren, Hendrik; Giovannetti, Elisa; Tang, Dean G.; Bruno, Tullia C.; Luo, Peng; Andersen, Mads H.; Qian, Bin-Zhi; Ishihara, Jun; Radisky, Derek C.; Elias, Salem; Yadav, Saurabh; Kim, Minah; Robert, Caroline; Diana, Patrizia; Schalper, Kurt A.; Shi, Tao; Merghoub, Taha; Krebs, Simone; Kusumbe, Anjali P.; Davids, Matthew S.; Brown, Jennifer R.; Kumar, Alan P.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and invasiveness and promote metastasis and cancer progression.

By targeting various components of the TME, novel investigational strategies aim to disrupt the TME’s contribution to the EMT, thereby improving treatment efficacy, addressing therapeutic resistance, and offering a nuanced approach to cancer therapy. This review scrutinizes the key players in the TME and the TME's contribution to the EMT, emphasizing avenues to therapeutically disrupt the interactions between the various TME components. Moreover, the article discusses the TME’s implications for resistance mechanisms and highlights the current therapeutic strategies toward TME modulation along with potential caveats.

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Also Published In

Title
Journal of Hematology & Oncology
DOI
https://doi.org/10.1186/s13045-024-01634-6

More About This Work

Academic Units
Irving Comprehensive Cancer Center
Published Here
April 2, 2025

Notes

Cancer, Tumor microenvironment (TME), T-cells, B-cells, tumor-associated macrophages
(TAMs), Natural killer (NK) cells, Myeloid-derived suppressor cells (MDSCs), Tumor-associated neutrophils (TANs), Dendritic cells (DCs), Cancer-associated fibroblasts (CAFs), Extracellular matrix (ECM), Chimeric antigen-receptor (CAR) T-cell therapy, T-cell receptor (TCR) therapy, Metastasis, Epithelial-mesenchymal transition (EMT), Theranostics