Cancer drug resistance induced by EMT: novel therapeutic strategies

被引:151
作者
De las Rivas, Javier [1 ]
Brozovic, Anamaria [2 ]
Izraely, Sivan [3 ]
Casas-Pais, Alba [4 ,5 ]
Witz, Isaac P. [3 ]
Figueroa, Angelica [4 ,5 ]
机构
[1] Univ Salamanca USAL, Canc Res Ctr CiC,IBMCC, CSIC,USAL,IBSAL,Consejo Super Invest Cient CSIC, Bioinformat & Funct Genom Grp, Salamanca, Spain
[2] Rudjer Boskovic Inst, Div Mol Biol, Bijenicka 54, Zagreb 10000, Croatia
[3] Tel Aviv Univ, George S Wise Fac Life Sci, Shmunis Sch Biomed & Canc Res, Tel Aviv, Israel
[4] Complexo Hosp Univ A Coruna CHUAC, Inst Invest Biomed A Coruna INIBIC, Epithelial Plastic & Metastasis Grp, Sergas, Spain
[5] Univ Coruna UDC, Coruna, Spain
关键词
Epithelial plasticity; Cancer; Therapy resistance; Tumour microenvironment; EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR-ASSOCIATED MACROPHAGES; TRANSCRIPTION FACTOR SNAIL; TGF-BETA; LUNG-CANCER; STEM-CELLS; GENE-EXPRESSION; MIR-200; FAMILY; EXTRACELLULAR-MATRIX; INDUCED APOPTOSIS;
D O I
10.1007/s00204-021-03063-7
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Over the last decade, important clinical benefits have been achieved in cancer patients by using drug-targeting strategies. Nevertheless, drug resistance is still a major problem in most cancer therapies. Epithelial-mesenchymal plasticity (EMP) and tumour microenvironment have been described as limiting factors for effective treatment in many cancer types. Moreover, epithelial-to-mesenchymal transition (EMT) has also been associated with therapy resistance in many different preclinical models, although limited evidence has been obtained from clinical studies and clinical samples. In this review, we particularly deepen into the mechanisms of which intermediate epithelial/mesenchymal (E/M) states and its interconnection to microenvironment influence therapy resistance. We also describe how the use of bioinformatics and pharmacogenomics will help to figure out the biological impact of the EMT on drug resistance and to develop novel pharmacological approaches in the future.
引用
收藏
页码:2279 / 2297
页数:19
相关论文
共 223 条
[1]   MicroRNA Regulation of Epithelial to Mesenchymal Transition [J].
Abba, Mohammed L. ;
Patil, Nitin ;
Leupold, Joerg Hendrik ;
Allgayer, Heike .
JOURNAL OF CLINICAL MEDICINE, 2016, 5 (01)
[2]   Interaction between non-small-cell lung cancer cells and fibroblasts via enhancement of TGF-β signaling by IL-6 [J].
Abulaiti, Abulimiti ;
Shintani, Yasushi ;
Funaki, Soichiro ;
Nakagiri, Tomoyuki ;
Inoue, Masayohi ;
Sawabata, Noriyoshi ;
Minami, Masato ;
Okumura, Meinoshin .
LUNG CANCER, 2013, 82 (02) :204-213
[3]   Transforming growth factor-β signaling: Tumorigenesis and targeting for cancer therapy [J].
Ahmadi, Amirhossein ;
Najafi, Masoud ;
Farhood, Bagher ;
Mortezaee, Keywan .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (08) :12173-12187
[4]   Upholding a role for EMT in pancreatic cancer metastasis [J].
Aiello, Nicole M. ;
Brabletz, Thomas ;
Kang, Yibin ;
Angela Nieto, M. ;
Weinberg, Robert A. ;
Stanger, Ben Z. .
NATURE, 2017, 547 (7661) :E7-E8
[5]   The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets [J].
Allard, Bertrand ;
Longhi, Maria Serena ;
Robson, Simon C. ;
Stagg, John .
IMMUNOLOGICAL REVIEWS, 2017, 276 (01) :121-144
[6]   EMT: 2016 [J].
Angela Nieto, M. ;
Huang, Ruby Yun-Ju ;
Jackson, Rebecca A. ;
Thiery, Jean Paul .
CELL, 2016, 166 (01) :21-45
[7]   Clinical implications of epithelial cell plasticity in cancer progression [J].
Aparicio, Luis A. ;
Blanco, Moises ;
Castosa, Raquel ;
Concha, Angel ;
Valladares, Manuel ;
Calvo, Lourdes ;
Figueroa, Angelica .
CANCER LETTERS, 2015, 366 (01) :1-10
[8]   Posttranscriptional regulation by RNA-binding proteins during epithelial-to-mesenchymal transition [J].
Aparicio, Luis A. ;
Abella, Vanessa ;
Valladares, Manuel ;
Figueroa, Angelica .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2013, 70 (23) :4463-4477
[9]   Biological influence of Hakai in cancer: a 10-year review [J].
Aparicio, Luis A. ;
Valladares, Manuel ;
Blanco, Moises ;
Alonso, Guillermo ;
Figueroa, Angelica .
CANCER AND METASTASIS REVIEWS, 2012, 31 (1-2) :375-386
[10]   Mining Drug-Target Associations in Cancer: Analysis of Gene Expression and Drug Activity Correlations [J].
Arroyo, Monica M. ;
Berral-Gonzalez, Alberto ;
Bueno-Fortes, Santiago ;
Alonso-Lopez, Diego ;
De Las Rivas, Javier .
BIOMOLECULES, 2020, 10 (05)