Journal of Hematology & Oncology (Jan 2025)
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition
- Antonino Glaviano,
- Hannah Si-Hui Lau,
- Lukas M. Carter,
- E. Hui Clarissa Lee,
- Hiu Yan Lam,
- Elena Okina,
- Donavan Jia Jie Tan,
- Wency Tan,
- Hui Li Ang,
- Daniela Carbone,
- Michelle Yi-Hui Yee,
- Muthu K. Shanmugam,
- Xiao Zi Huang,
- Gautam Sethi,
- Tuan Zea Tan,
- Lina H. K. Lim,
- Ruby Yun-Ju Huang,
- Hendrik Ungefroren,
- Elisa Giovannetti,
- Dean G. Tang,
- Tullia C. Bruno,
- Peng Luo,
- Mads Hald Andersen,
- Bin-Zhi Qian,
- Jun Ishihara,
- Derek C. Radisky,
- Salem Elias,
- Saurabh Yadav,
- Minah Kim,
- Caroline Robert,
- Patrizia Diana,
- Kurt A. Schalper,
- Tao Shi,
- Taha Merghoub,
- Simone Krebs,
- Anjali P. Kusumbe,
- Matthew S. Davids,
- Jennifer R. Brown,
- Alan Prem Kumar
Affiliations
- Antonino Glaviano
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo
- Hannah Si-Hui Lau
- Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore
- Lukas M. Carter
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center
- E. Hui Clarissa Lee
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- Hiu Yan Lam
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- Elena Okina
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- Donavan Jia Jie Tan
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- Wency Tan
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- Hui Li Ang
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- Daniela Carbone
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo
- Michelle Yi-Hui Yee
- Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore
- Muthu K. Shanmugam
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- Xiao Zi Huang
- Cancer Science Institute of Singapore, National University of Singapore
- Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- Tuan Zea Tan
- Cancer Science Institute of Singapore, National University of Singapore
- Lina H. K. Lim
- Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore
- Ruby Yun-Ju Huang
- School of Medicine and Graduate Institute of Oncology, College of Medicine, National Taiwan University
- Hendrik Ungefroren
- First Department of Medicine, University Hospital Schleswig-Holstein (UKSH)
- Elisa Giovannetti
- Department of Medical Oncology, Cancer Center Amsterdam, UMC, Vrije Universiteit, HV Amsterdam
- Dean G. Tang
- Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center
- Tullia C. Bruno
- Department of Immunology, School of Medicine, University of Pittsburgh
- Peng Luo
- Department of Oncology, Zhujiang Hospital, Southern Medical University
- Mads Hald Andersen
- National Center for Cancer Immune Therapy, Department of Oncology, Herlev and Gentofte Hospital
- Bin-Zhi Qian
- Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, The Human Phenome Institute, Zhangjiang-Fudan International Innovation Center, Fudan University
- Jun Ishihara
- Department of Bioengineering, Imperial College London
- Derek C. Radisky
- Department of Cancer Biology, Mayo Clinic
- Salem Elias
- Dana-Farber Cancer Institute, Harvard Medical School
- Saurabh Yadav
- Dana-Farber Cancer Institute, Harvard Medical School
- Minah Kim
- Herbert Irving Comprehensive Cancer Center, Columbia University
- Caroline Robert
- Department of Cancer Medicine, Inserm U981, Gustave Roussy Cancer Center, Université Paris-Saclay
- Patrizia Diana
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo
- Kurt A. Schalper
- Department of Pathology, Yale School of Medicine, Yale University
- Tao Shi
- Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine
- Taha Merghoub
- Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine
- Simone Krebs
- Department of Radiology, Memorial Sloan Kettering Cancer Center
- Anjali P. Kusumbe
- Tissue and Tumor Microenvironment Group, MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Matthew S. Davids
- Dana-Farber Cancer Institute, Harvard Medical School
- Jennifer R. Brown
- Dana-Farber Cancer Institute, Harvard Medical School
- Alan Prem Kumar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
- DOI
- https://doi.org/10.1186/s13045-024-01634-6
- Journal volume & issue
-
Vol. 18,
no. 1
pp. 1 – 96
Abstract
Abstract 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.
Keywords
- 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)
