Targeting the Colorectal Cancer Stem Cell
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Two recent studies in mice show that, on ablation of colon cancer stem cells, differentiated cancer cells can dedifferentiate to supply a new pool of cancer stem cells, and extracellular signals have a role in this process.
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Metabolic remodelling, cancer stem cells and epithelial-to-mesenchymal transition promote resistance to targeted therapy.
“Recently, metabolic remodelling, CSCs and EMT have also been confirmed to promote resistance to targeted therapy (Fig. 1).”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [16]
Intrinsic mechanisms of metabolism, autophagy, cancer stem cells and epithelial-to-mesenchymal transition are correlated with poor progression despite anti-EGFR monoclonal antibody treatment.
“In recent years, the intrinsic mechanisms of metabolism, autophagy [15], cancer stem cells (CSCs) [16] and epithelial-to-mesenchymal transition (EMT )[17] have also been confirmed to be correlated with poor progression despite anti-EGFR mAb treatment.”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [16]
Cites
Cancer Stem Cells: Basic Concepts and Therapeutic Implications
Nassar, D., & Blanpain, C. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044438 · Cited by 869 · see citing works
A distinct role for Lgr5+ stem cells in primary and metastatic colon cancer
Melo, F. D. S. E., Kurtova, A. V., Harnoss, J. M., Kljavin, N. M., Hoeck, J. D., Hung, J., Anderson, J. E., Storm, E. E., Modrusan, Z. D., Koeppen, H., et al. (2017) · Nature · doi:10.1038/nature21713 · Cited by 782 · see citing works
Cancer stem cells: The challenges ahead
Medema, J. P. (2013) · Nature Cell Biology · doi:10.1038/ncb2717 · Cited by 740 · see citing works
Self-citationVisualization and targeting of LGR5+ human colon cancer stem cells
Shimokawa, M., Ohta, Y., Nishikori, S., Matano, M., Takano, A., Fujii, M., Date, S., Sugimoto, S., Kanai, T., & Sato, T. (2017) · Nature · doi:10.1038/nature22081 · Cited by 728 · see citing works
Microenvironmental regulation of stem cells in intestinal homeostasis and cancer
Medema, J. P., & Vermeulen, L. (2011) · Nature · doi:10.1038/nature10212 · Cited by 470 · see citing works
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Cancer stem cells (CSCs) in cancer progression and therapy
Najafi, M., Farhood, B., & Mortezaee, K. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27740 · Cited by 578 · see citing works
Nano-Based Approved Pharmaceuticals for Cancer Treatment: Present and Future Challenges
Rodríguez, F., Caruana, P., de la Fuente, N., Español, P., Gámez, M., Balart, J., Llurba, E., Rovira, R., Ruiz, R., Martín-Lorente, C., et al. (2022) · Biomolecules · doi:10.3390/biom12060784 · Cited by 281 · see citing works
Zhou, J., Ji, Q., & Li, Q. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02130-2 · Cited by 246 · see citing works
MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside
To, K. K. W., Tong, C. W. S., Wu, M., & Cho, W. C. S. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i27.2949 · Cited by 195 · see citing works
α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer
Tran, T. Q., Hanse, E. A., Habowski, A. N., Li, H., Ishak Gabra, M. B., Yang, Y., Lowman, X. H., Ooi, A. M., Liao, S. Y., Edwards, R. A., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0035-5 · Cited by 161 · see citing works
Role of Epithelial to Mesenchymal Transition in Colorectal Cancer
Lu, J., Kornmann, M., & Traub, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914815 · Cited by 148 · see citing works
Zheng, H., Liu, H., Li, H., Dou, W., Wang, J., Zhang, J., Liu, T., Wu, Y., Liu, Y., & Wang, X. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02913-0 · Cited by 139 · see citing works
The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials
Hervieu, C., Christou, N., Battu, S., & Mathonnet, M. (2021) · Cancers · doi:10.3390/cancers13051092 · Cited by 108 · see citing works
Targeting Gastric Cancer Stem Cells to Enhance Treatment Response
Rao, X., Zhang, C., Luo, H., Zhang, J., Zhuang, Z., Liang, Z., & Wu, X. (2022) · Cells · doi:10.3390/cells11182828 · Cited by 94 · see citing works
Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery
Di Franco, S., Bianca, P., Sardina, D. S., Turdo, A., Gaggianesi, M., Veschi, V., Nicotra, A., Mangiapane, L. R., Lo Iacono, M., Pillitteri, I., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25333-9 · Cited by 80 · see citing works
Self-citationSong, S., Chen, Q., Li, Y., Lei, G., Scott, A. W., Huo, L., Li, C. Y., Estrella, J. S., Correa, A. M., Pizzi, M. P., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-321175 · Cited by 62 · see citing works
Explaining the unexplainable: discrepancies in results from the CALGB/SWOG 80405 and FIRE-3 studies
Aderka, D., Stintzing, S., & Heinemann, V. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30172-x · Cited by 55 · see citing works
Fujishita, T., Kojima, Y., Kajino‐Sakamoto, R., Mishiro‐Sato, E., Shimizu, Y., Hosoda, W., Yamaguchi, R., Taketo, M. M., & Aoki, M. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-1369 · Cited by 53 · see citing works
Lv, L., Li, Q., Chen, S., Zhang, X., Tao, X., Tang, X., Wang, S., Che, G., Yu, Y., & He, L. (2019) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.111597 · Cited by 52 · see citing works
Zhang, M., Xu, C., Wang, H., Peng, Y., Li, H.-O., Zhou, Y., Liu, S., Wang, F., Liu, L., Chang, Y., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1309-7 · Cited by 48 · see citing works
Zhang, J., Ying, Y., Li, M., Wang, M., Huang, X., Jia, M., Zeng, J., Ma, C., Zhang, Y., Li, C., et al. (2020) · Theranostics · doi:10.7150/thno.47081 · Cited by 48 · see citing works
Guo, M., You, C., & Dou, J. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.08.109 · Cited by 38 · see citing works
Bamodu, O. A., Yang, C.-K., Cheng, W.-H., Tzeng, D. T. W., Kuo, K.-T., Huang, C.-C., Deng, L., Hsiao, M., Lee, W., & Yeh, C. (2018) · Cancers · doi:10.3390/cancers10080269 · Cited by 36 · see citing works
Lee, P.-J., Ho, C., Ho, H. H., Chen, W.-J., Lin, C.-H., Lai, Y., Juan, Y., Chu, W.-C., Lee, J.-H., Su, S., et al. (2021) · Theranostics · doi:10.7150/thno.62676 · Cited by 33 · see citing works
Chang, Y.-H., Zhang, J., Huo, X., Qu, X., Xia, C., Huang, K., Xie, F., Wang, N., Wei, X., & Jia, Q. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110390 · Cited by 33 · see citing works
KMT9 Controls Stemness and Growth of Colorectal Cancer
Berlin, C., Cottard, F., Willmann, D., Urban, S., Tirier, S. M., Marx, L., Rippe, K., Schmitt, M., Petrocelli, V., Greten, F. R., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1261 · Cited by 32 · see citing works
Cheng, C., Liao, P.-N., Ho, A., Lim, K., Chang, J., Su, Y.-W., Chen, C. G., Chiang, Y.-W., Yang, B.-L., Lin, H., et al. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0456-y · Cited by 31 · see citing works
Elevated transcription and glycosylation of B3GNT5 promotes breast cancer aggressiveness
Miao, Z., Cao, Q., Liao, R., Chen, X., Li, X., Bai, L., Ma, C., Deng, X., Dai, Z., Li, J., et al. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02375-5 · Cited by 31 · see citing works
Jing, B., Guo, F., An, R. F., Gao, Y., Li, Y., Xie, Y., Wang, J., Chen, Y., Li, H., Gao, T., et al. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-01792-8 · Cited by 25 · see citing works
Guo, M., Luo, B., Pan, M., Li, M., Xu, H., Zhao, F., & Dou, J. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106850 · Cited by 25 · see citing works
Cancer stem cells modulate patterns and processes of evolution in cancers
Laplane, L. (2018) · Biology & Philosophy · doi:10.1007/s10539-018-9629-z · Cited by 24 · see citing works
Sun, R., Sun, C., Yue, Z., Yin, G., Zhou, L., Zhang, S., Zhang, Y., Tang, D.-C., & Tan, X. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155824 · Cited by 19 · see citing works
Characteristic Analysis of Featured Genes Associated With Stemness Indices in Colorectal Cancer
Lu, Y., Zhou, X., Liu, Z., Wang, W., Li, F., & Fu, W. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.563922 · Cited by 17 · see citing works
Zhao, H., Su, W., sun, Y., & Wu, Z. (2020) · Biochemical Genetics · doi:10.1007/s10528-020-09949-y · Cited by 16 · see citing works
The Pluripotency Network in Colorectal Cancer Pathogenesis and Prognosis: an Update
Voutsadakis, I. A. (2018) · Biomarkers in Medicine · doi:10.2217/bmm-2017-0369 · Cited by 16 · see citing works
Guo, M., You, C., Dong, W., Luo, B., Wu, Y.-H., Chen, Y., Li, J., Pan, M., Li, M., Zhao, F., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110804 · Cited by 14 · see citing works
Li, F., Zhou, Y., Lin, X., Zhang, Y., Hu, Q., Zhao, E., Li, H. ‐., Pan, X., Shu, F., Zhang, K., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-024-06001-0 · Cited by 13 · see citing works
Suppression of cancer stemness by upregulating Ligand-of-Numb protein X1 in colorectal carcinoma
Ma, L., Wang, L., Shan, Y., Nafees, M., Elshoura, I., Zhang, R., Wang, F., & Yin, W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188665 · Cited by 11 · see citing works
Wang, L., Deng, K., Gong, L., Zhou, L., Sayed, S., Li, H., Sun, Q., Su, Z., Wang, Z., Liu, S., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104955 · Cited by 11 · see citing works
Husain, K. M., Coppola, D., Yang, C. S., & Malafa, M. P. (2024) · Carcinogenesis · doi:10.1093/carcin/bgae041 · Cited by 9 · see citing works
Zhong, L., Tan, W., Yang, Q., Zou, Z., Zhou, R., Huang, Y., Qiu, Z., Zheng, K., & Huang, Z.-H. (2022) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo-22-1137 · Cited by 9 · see citing works
Guan, S., Wu, C., Liao, T.-Z., Luo, T., Lin, K., & Liu, S. (2020) · EJNMMI Research · doi:10.1186/s13550-020-0597-3 · Cited by 9 · see citing works
Shinji, S., Sasaki, N., Yamada, T., Koizumi, M., Ohta, R., Matsuda, A., Yokoyama, Y., Takahashi, G., Hotta, M., Hara, K., et al. (2019) · Cancer Science · doi:10.1111/cas.14221 · Cited by 8 · see citing works
Chang, J. Y., Kim, J. H., Kang, J., Park, Y., Park, S. J., Cheon, J. H., Kim, W. H., Kim, H., Park, J. J., & Kim, T. I. (2020) · Yonsei Medical Journal · doi:10.3349/ymj.2020.61.7.572 · Cited by 7 · see citing works
Shayimu, P., Yusufu, A., Rehemutula, A., Redati, D., Jiapaer, R., & Tuerdi, R. (2020) · Technology in Cancer Research & Treatment · doi:10.1177/1533033820967475 · Cited by 7 · see citing works
Zheng, L., Lu, J., Kong, D., & Zhan, Y. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e35549 · Cited by 6 · see citing works
CANDiT: A machine learning framework for differentiation therapy in colorectal cancer
Sinha, S., Alcantara, J. A., Perry, K., Castillo, V., Ondersma, A. K., Banerjee, S., McLaren, E., Espinoza, C. R., Taheri, S., Vidales, E., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102421 · Cited by 5 · see citing works
Zhu, M., Yu, R., Liu, Y., Geng, X., Liu, Q., Liu, S., Zhu, Y., Li, G., Guo, Y., Xi, X., et al. (2024) · Biochemical Genetics · doi:10.1007/s10528-023-10627-y · Cited by 5 · see citing works
STAT3‐mediated gene expression in colorectal cancer cells‐derived cancer stem‐like tumorspheres
Lin, H., Ho, A., Huang, H., Yang, B., Shih, B., Lin, H., Yeh, C., Hsu, C., & Cheng, C. (2020) · Advances in digestive medicine · doi:10.1002/aid2.13223 · Cited by 4 · see citing works
Yan, C., Liu, S., Song, Q., & Hu, Y. (2023) · PubMed Central · doi:10.12122/j.issn.1673-4254.2023.08.03 · Cited by 4 · see citing works
Guo, F., Yang, T., Guo, R., & Wang, Y. (2021) · Neoplasma · doi:10.4149/neo_2021_200714n726 · Cited by 3 · see citing works
Sun, Q. L., Liu, B., Lan, Q., Su, Z., Fu, Q., Wang, L. Y., Deng, Y., Li, C., Xue, V. W., Liu, S., et al. (2023) · International Journal of Oncology · doi:10.3892/ijo.2023.5569 · Cited by 3 · see citing works
Expression of CD44 is regulated by ELF3 in 5-FU treated colorectal cancer cells
Li, F., Qiu, F., Xu, F., Yu, Q., Liu, S., Guo, Y., Zhu, Y., Xi, X., & Du, B. (2023) · Gene · doi:10.1016/j.gene.2023.147896 · Cited by 3 · see citing works
Frank, N. Y., Illert, B., Frank, M. H., Germer, C. T., Gasser, M., Grimmig, T., Rosenwald, A., Kim, M., Moench, R., Gasser, D. A. M. W., et al. (2017) · Journal of Cancer Science & Therapy · doi:10.4172/1948-5956.1000490 · Cited by 3 · see citing works
Arai, H., Millstein, J., Loupakis, F., Stintzing, S., Wang, J., Battaglin, F., Kawanishi, N., Jayachandran, P., Soni, S., Zhang, W., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.03.048 · Cited by 2 · see citing works
Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Cheng, C., Hsu, P., Sie, Z., & Chen, G. T. Y. (2020) · Journal of Visualized Experiments · doi:10.3791/61077 · Cited by 1 · see citing works
Machine Learning–Guided Differentiation Therapy Targets Cancer Stem Cells in Colorectal CancersPreprint
Sinha, S., Alcantara, J. A., Perry, K., Castillo, V., Ondersma, A., Banerjee, S., McLaren, E., Espinoza, C. R., Taheri, S., Vidales, E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.13.557628 · Cited by 1 · see citing works
Data from KMT9 Controls Stemness and Growth of Colorectal Cancer
Berlin, C., Cottard, F., Willmann, D., Urban, S., Tirier, S. M., Marx, L., Rippe, K., Schmitt, M., Petrocelli, V., Greten, F. R., et al. (2023) · doi:10.1158/0008-5472.c.6513688.v1
Zheng, H., Liu, H., Li, H., Dou, W., Wang, J., Zhang, J., Liu, T., Wu, Y., Liu, Y., & Wang, X. (2022) · Figshare · doi:10.6084/m9.figshare.20046957
An overview of nanotherapeutics and nanodiagnostics
Rudrangi, S. R. S., Basavaraj, H., Pawar, A. K., Rajendran, S. P., Velaga, V. S. S. R., & Tiwari, G. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-28836-4.00002-0 · Cited by 1 · see citing works
Miao, Z., Cao, Q., Liao, R., Chen, X., Li, X., Bai, L., Ma, C., Deng, X., Dai, Z., Li, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19728319
Miao, Z., Cao, Q., Liao, R., Chen, X., Li, X., Bai, L., Ma, C., Deng, X., Dai, Z., Li, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19728322
Miao, Z., Cao, Q., Liao, R., Chen, X., Li, X., Bai, L., Ma, C., Deng, X., Dai, Z., Li, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19728313
Miao, Z., Cao, Q., Liao, R., Chen, X., Li, X., Bai, L., Ma, C., Deng, X., Dai, Z., Li, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19728325
Jing, B., Guo, F., An, R., Gao, Y., Li, Y., Xie, Y., Wang, J., Chen, Y., Li, H., Gao, T., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26565767
Zheng, H., Liu, H., Li, H., Dou, W., Wang, J., Zhang, J., Liu, T., Wu, Y., 刘玉村, & Wang, X. (2022) · Figshare · doi:10.6084/m9.figshare.20046954
Miao, Z., Cao, Q., Liao, R., Chen, X., Li, X., Bai, L., Ma, C., Deng, X., Dai, Z., Li, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19728316
Miao, Z., Cao, Q., Liao, R., Chen, X., Li, X., Bai, L., Ma, C., Deng, X., Dai, Z., Li, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19728310
Self-fueling catalysis-driven membrane destabilization triggers CSC-enriched tumors ablation
Huang, L., Hu, B., Wu, G., Ma, W., Qiu, J., Zhu, J., Yang, J., Cai, H., Fan, Q., Ren, B., et al. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04558-0
- Authors
- Medema, J. P.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Medema, Jan Paul
- ORCID
- Medema, Jan Paul
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-08-31
- Volume
- 377
- Issue
- 9
- Pages
- 888-890
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2752213732
- Cited by
- 63
- References
- 5
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 14 · 2021: 8 · 2020: 12 · 2019: 4 · 2018: 7 · 2017: 2
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- colorectal cancer, cancer stem cells, dedifferentiation, extracellular signals, tumor heterogeneity
- MeSH terms
- Cetuximab, Animals, Antineoplastic Agents, Colon, Disease Models, Animal, Humans, Neoplastic Stem Cells, Colorectal Neoplasms, Receptors, G-Protein-Coupled, Mice, Cell Dedifferentiation, Gene Knock-In Techniques, Molecular Targeted Therapy
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