Review Article | Published:

Organoids in cancer research

Nature Reviews Cancervolume 18pages407418 (2018) | Download Citation

Abstract

The recent advances in in vitro 3D culture technologies, such as organoids, have opened new avenues for the development of novel, more physiological human cancer models. Such preclinical models are essential for more efficient translation of basic cancer research into novel treatment regimens for patients with cancer. Wild-type organoids can be grown from embryonic and adult stem cells and display self-organizing capacities, phenocopying essential aspects of the organs they are derived from. Genetic modification of organoids allows disease modelling in a setting that approaches the physiological environment. Additionally, organoids can be grown with high efficiency from patient-derived healthy and tumour tissues, potentially enabling patient-specific drug testing and the development of individualized treatment regimens. In this Review, we evaluate tumour organoid protocols and how they can be utilized as an alternative model for cancer research.

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References

  1. 1.

    Torre, L. A. et al. Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87–108 (2015).

  2. 2.

    Kamb, A. What’s wrong with our cancer models? Nat. Rev. Drug Discov. 4, 161–165 (2005).

  3. 3.

    Caponigro, G. & Sellers, W. R. Advances in the preclinical testing of cancer therapeutic hypotheses. Nat. Rev. Drug Discov. 10, 179–187 (2011).

  4. 4.

    Cheon, D. J. & Orsulic, S. Mouse models of cancer. Annu. Rev. Pathol. 6, 95–119 (2011).

  5. 5.

    Liu, X. et al. ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. Am. J. Pathol. 180, 599–607 (2012).

  6. 6.

    Ben-David, U. et al. Patient-derived xenografts undergo mouse-specific tumor evolution. Nat. Genet. 49, 1567–1575 (2017).

  7. 7.

    Byrne, A. T. et al. Interrogating open issues in cancer medicine with patient-derived xenografts. Nat. Rev. Cancer. 17, 254–268 (2017).

  8. 8.

    Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009). Sato and colleagues describe the generation of organoids from mouse intestinal stem cells, which initiated the development of many other adult stem cell-derived organoid culture protocols.

  9. 9.

    Carmon, K. S., Gong, X., Lin, Q., Thomas, A. & Liu, Q. R-Spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc. Natl Acad. Sci. USA 108, 11452–11457 (2011).

  10. 10.

    de Lau, W. et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476, 293–297 (2011).

  11. 11.

    Sato, T. et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141, 1762–1772 (2011). This paper describes the generation and long-term expansion of patient-derived organoids from normal and cancerous colon tissue.

  12. 12.

    Jung, P. et al. Isolation and in vitro expansion of human colonic stem cells. Nat. Med. 17, 1225–1227 (2011). This paper describes the establishment of human colon organoids from a single cell.

  13. 13.

    Huch, M. et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160, 299–312 (2015).

  14. 14.

    Boj, S. F. et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 160, 324–338 (2015).

  15. 15.

    Karthaus, W. R. et al. Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell 159, 163–175 (2014).

  16. 16.

    Chua, C. W. et al. Single luminal epithelial progenitors can generate prostate organoids in culture. Nat. Cell Biol. 16, 951–961 (2014).

  17. 17.

    Bartfeld, S. et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148, 126–136 e126 (2015).

  18. 18.

    Kessler, M. et al. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nat. Commun. 6, 8989 (2015).

  19. 19.

    Ren, W. et al. Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo. Proc. Natl Acad. Sci. USA 111, 16401–16406 (2014).

  20. 20.

    Maimets, M. et al. Long-term in vitro expansion of salivary gland stem cells driven by wnt signals. Stem Cell Rep. 6, 150–162 (2016).

  21. 21.

    DeWard, A. D., Cramer, J. & Lagasse, E. Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep. 9, 701–711 (2014).

  22. 22.

    Rock, J. R. et al. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc. Natl Acad. Sci. USA 106, 12771–12775 (2009).

  23. 23.

    Turco, M. Y. et al. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nat. Cell Biol. 19, 568–577 (2017).

  24. 24.

    Sachs, N. et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell 172, 373–386.e10 (2017).

  25. 25.

    Clevers, H. Modeling development and disease with organoids. Cell 165, 1586–1597 (2016).

  26. 26.

    Ootani, A. et al. Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat. Med. 15, 701–706 (2009). Ootani and colleagues develop an organoid culture system for intestinal epithelium using an air–liquid interface and underlying stromal elements.

  27. 27.

    Papapetrou, E. P. Patient-derived induced pluripotent stem cells in cancer research and precision oncology. Nat. Med. 22, 1392–1401 (2016).

  28. 28.

    van de Wetering, M. et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933–945 (2015). This paper describes the generation of the first organoid biobank consisting of primary tumour and matching healthy organoids from patients with CRC.

  29. 29.

    Fujii, M. et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 18, 827–838 (2016).

  30. 30.

    Huang, L. et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat. Med. 21, 1364–1371 (2015).

  31. 31.

    Broutier, L. et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat. Med. 23, 1424–1435 (2017).

  32. 32.

    Weeber, F. et al. Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases. Proc. Natl Acad. Sci. USA 112, 13308–13311 (2015).

  33. 33.

    Gao, D. et al. Organoid cultures derived from patients with advanced prostate cancer. Cell 159, 176–187 (2014).

  34. 34.

    Drost, J. et al. Organoid culture systems for prostate epithelial and cancer tissue. Nat. Protoc. 11, 347–358 (2016).

  35. 35.

    Drost, J. et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature 521, 43–47 (2015). Starting from healthy colon organoids, Drost and colleagues use CRISPR technology to introduce common CRC mutations and study tumour progression and chromosome instability.

  36. 36.

    Verissimo, C. S. et al. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening. eLife 5, pii: e18489 (2016).

  37. 37.

    Cancer Genome Atlas, N. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487, 330–337 (2012).

  38. 38.

    Sakamoto, N. et al. BRAFV600E cooperates with CDX2 inactivation to promote serrated colorectal tumorigenesis. eLife 6, pii: e20331 (2017).

  39. 39.

    Kondo, J. et al. Retaining cell-cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. Proc. Natl Acad. Sci. USA 108, 6235–6240 (2011).

  40. 40.

    Chen, B. et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat. Chem. Biol. 5, 100–107 (2009).

  41. 41.

    Hao, H. X. et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 485, 195–200 (2012).

  42. 42.

    Koo, B. K. et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature 488, 665–669 (2012).

  43. 43.

    Cristobal, A. et al. Personalized proteome profiles of healthy and tumor human colon organoids reveal both individual diversity and basic features of colorectal cancer. Cell Rep. 18, 263–274 (2017).

  44. 44.

    Schutte, M. et al. Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors. Nat. Commun. 8, 14262 (2017).

  45. 45.

    Seino, T. et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell 22, 454–467.e6 (2018).

  46. 46.

    Barretina, J. et al. The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603–607 (2012).

  47. 47.

    Vlachogiannis, G. et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359, 920–926 (2018). In this paper, Vlachogiannis and colleagues describe for the first time that drug responses in patient-derived tumour organoids recapitulate patient responses in the clinic.

  48. 48.

    Shenoy, T. R. et al. CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair. Ann. Oncol. 28, 1495–1507 (2017).

  49. 49.

    Crespo, M. et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nat. Med. 23, 878–884 (2017).

  50. 50.

    Ballet, F. Hepatotoxicity in drug development: detection, significance and solutions. J. Hepatol. 26 (Suppl. 2), 26–36 (1997).

  51. 51.

    Meng, Q. Three-dimensional culture of hepatocytes for prediction of drug-induced hepatotoxicity. Expert Opin. Drug Metab. Toxicol. 6, 733–746 (2010).

  52. 52.

    Katsuda, T. et al. Conversion of terminally committed hepatocytes to culturable bipotent progenitor cells with regenerative capacity. Cell Stem Cell 20, 41–55 (2016).

  53. 53.

    Eder, A., Vollert, I., Hansen, A. & Eschenhagen, T. Human engineered heart tissue as a model system for drug testing. Adv. Drug Deliv. Rev. 96, 214–224 (2016).

  54. 54.

    Voges, H. K. et al. Development of a human cardiac organoid injury model reveals innate regenerative potential. Development 144, 1118–1127 (2017).

  55. 55.

    Takasato, M. et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526, 564–568 (2015).

  56. 56.

    Dekkers, J. F. et al. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat. Med. 19, 939–945 (2013).

  57. 57.

    Dekkers, J. F. et al. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis. Sci Transl Med 8, 344ra384 (2016).

  58. 58.

    Groenendijk, F. H. & Bernards, R. Drug resistance to targeted therapies: deja vu all over again. Mol. Oncol. 8, 1067–1083 (2014).

  59. 59.

    Bernards, R. A missing link in genotype-directed cancer therapy. Cell 151, 465–468 (2012).

  60. 60.

    Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).

  61. 61.

    Chen, D. S. & Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 541, 321–330 (2017).

  62. 62.

    Van Allen, E. M. et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350, 207–211 (2015).

  63. 63.

    Rizvi, N. A. et al. Cancer immunology. mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124–128 (2015).

  64. 64.

    Sato, T. & Clevers, H. Snapshot: growing organoids from stem cells. Cell 161, 1700–1700 e1 (2015).

  65. 65.

    Le, D. T. et al. PD-1 Blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 372, 2509–2520 (2015).

  66. 66.

    Nozaki, K. et al. Co-culture with intestinal epithelial organoids allows efficient expansion and motility analysis of intraepithelial lymphocytes. J. Gastroenterol. 51, 206–213 (2016).

  67. 67.

    Finnberg, N. K. et al. Application of 3D tumoroid systems to define immune and cytotoxic therapeutic responses based on tumoroid and tissue slice culture molecular signatures. Oncotarget 8, 66747–66757 (2017).

  68. 68.

    Zumwalde, N. A. et al. Analysis of immune cells from human mammary ductal epithelial organoids reveals Vdelta2+ T Cells that efficiently target breast carcinoma cells in the presence of bisphosphonate. Cancer Prev. Res. 9, 305–316 (2016).

  69. 69.

    Stronen, E. et al. Targeting of cancer neoantigens with donor-derived T cell receptor repertoires. Science 352, 1337–1341 (2016).

  70. 70.

    Tajima, A., Pradhan, I., Trucco, M. & Fan, Y. Restoration of thymus function with bioengineered thymus organoids. Curr. Stem Cell Rep. 2, 128–139 (2016).

  71. 71.

    De Flora, S. & Bonanni, P. The prevention of infection-associated cancers. Carcinogenesis 32, 787–795 (2011).

  72. 72.

    Salama, N. R., Hartung, M. L. & Muller, A. Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat. Rev. Microbiol. 11, 385–399 (2013).

  73. 73.

    Huang, J. Y. et al. Chemodetection and destruction of host urea allows Helicobacter pylori to locate the epithelium. Cell Host Microbe 18, 147–156 (2015).

  74. 74.

    McCracken, K. W. et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516, 400–404 (2014).

  75. 75.

    Scanu, T. et al. Salmonella manipulation of host signaling pathways provokes cellular transformation associated with gallbladder carcinoma. Cell Host Microbe 17, 763–774 (2015).

  76. 76.

    Yin, Y. et al. Modeling rotavirus infection and antiviral therapy using primary intestinal organoids. Antiviral Res. 123, 120–131 (2015).

  77. 77.

    Stratton, M. R., Campbell, P. J. & Futreal, P. A. The cancer genome. Nature 458, 719–724 (2009).

  78. 78.

    Behjati, S. et al. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513, 422–425 (2014). This study is the first to exploit genome sequencing of clonal organoids as a tool to study mutational processes.

  79. 79.

    Blokzijl, F. et al. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538, 260–264 (2016).

  80. 80.

    Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013).

  81. 81.

    Davies, H. et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat. Med. 23, 517–525 (2017).

  82. 82.

    Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005).

  83. 83.

    Fong, P. C. et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 361, 123–134 (2009).

  84. 84.

    Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).

  85. 85.

    Drost, J. et al. Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer. Science 358, 234–238 (2017).

  86. 86.

    Greenman, C. et al. Patterns of somatic mutation in human cancer genomes. Nature 446, 153–158 (2007).

  87. 87.

    McGranahan, N. & Swanton, C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 168, 613–628 (2017).

  88. 88.

    Pauli, C. et al. Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov. 7, 462–477 (2017).

  89. 89.

    Roerink, S. et al. A high-resolution molecular history of intra-cancer diversification. Nature https://doi.org/10.1038/s41586-018-0024-3 (2018).

  90. 90.

    Lugli, N. et al. Enhanced rate of acquisition of point mutations in mouse intestinal adenomas compared to normal tissue. Cell Rep. 19, 2185–2192 (2017).

  91. 91.

    Matano, M. et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat. Med. 21, 256–262 (2015).

  92. 92.

    Rajagopalan, H., Nowak, M. A., Vogelstein, B. & Lengauer, C. The significance of unstable chromosomes in colorectal cancer. Nat. Rev. Cancer 3, 695–701 (2003).

  93. 93.

    Fumagalli, A. et al. Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids. Proc. Natl Acad. Sci. USA 114, E2357–E2364 (2017).

  94. 94.

    Fumagalli, A. et al. A surgical orthotopic organoid transplantation approach in mice to visualize and study colorectal cancer progression. Nat. Protoc. 13, 235–247 (2018).

  95. 95.

    Li, X. et al. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat. Med. 20, 769–777 (2014).

  96. 96.

    Melo, F. S. et al. A distinct role for Lgr5+ stem cells in primary and metastatic colon cancer. Nature 543, 676–680 (2017).

  97. 97.

    O’Rourke, K. P. et al. Transplantation of engineered organoids enables rapid generation of metastatic mouse models of colorectal cancer. Nat. Biotechnol. 35, 577–582 (2017).

  98. 98.

    Roper, J. et al. In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Nat. Biotechnol. 35, 569–576 (2017).

  99. 99.

    Shimokawa, M. et al. Visualization and targeting of LGR5+ human colon cancer stem cells. Nature 545, 187–192 (2017). References 96 and 99 describe the use of intestinal organoids to study the contribution of CSCs to primary and metastatic CRC.

  100. 100.

    Wang, K. et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat. Genet. 46, 573–582 (2014).

  101. 101.

    Leggett, B. & Whitehall, V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology 138, 2088–2100 (2010).

  102. 102.

    Fessler, E. et al. TGFbeta signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype. EMBO Mol. Med. 8, 745–760 (2016).

  103. 103.

    Yan, H. H. et al. RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation. Gut 66, 1645–1656 (2016).

  104. 104.

    Schwank, G. et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13, 653–658 (2013).

  105. 105.

    Koo, B. K., van Es, J. H., van den Born, M. & Clevers, H. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43; Znrf3-mutant neoplasia. Proc. Natl Acad. Sci. USA 112, 7548–7550 (2015).

  106. 106.

    Nadauld, L. D. et al. Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer. Genome Biol. 15, 428 (2014).

  107. 107.

    Dow, L. E. et al. Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer. Cell 161, 1539–1552 (2015).

  108. 108.

    Yin, X. et al. Engineering stem cell organoids. Cell Stem Cell 18, 25–38 (2016).

  109. 109.

    Workman, M. J. et al. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat. Med. 23, 49–59 (2017).

  110. 110.

    Ohlund, D. et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 214, 579–596 (2017).

  111. 111.

    Gjorevski, N. et al. Designer matrices for intestinal stem cell and organoid culture. Nature 539, 560–564 (2016). In this paper, Gjorevski and colleagues engineer synthetic matrices supporting expansion of intestinal organoids, which hold great potential for the applications of organoids in regenerative medicine.

  112. 112.

    Janda, C. Y. et al. Surrogate Wnt agonists that phenocopy canonical Wnt and beta-catenin signalling. Nature 545, 234–237 (2017).

  113. 113.

    Mihara, E. et al. Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/alpha-albumin. eLife 5, pii: e11621 (2016).

  114. 114.

    Tuysuz, N. et al. Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells. Nat. Commun. 8, 14578 (2017).

  115. 115.

    Hubert, C. G. et al. A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and cancer stem cell heterogeneity of tumors found in vivo. Cancer Res. 76, 2465–2477 (2016).

  116. 116.

    Sachs, N. & Clevers, H. Organoid cultures for the analysis of cancer phenotypes. Curr. Opin. Genet. Dev. 24, 68–73 (2014).

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Acknowledgements

The authors thank K. Kretzschmar and J. Meijerink for critical reading of the manuscript. We are grateful for support from the Dutch Cancer Society (KWF) and the Alpe d’HuZes Bas Mulder Award to J.D. (KWF/Alpe d’HuZes, 10218) and for the support of Oncode Institute to H.C.

Author information

Affiliations

  1. Princess Máxima Centre for Paediatric Oncology, Utrecht, Netherlands

    • Jarno Drost
    •  & Hans Clevers
  2. Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, Netherlands

    • Hans Clevers
  3. Oncode Institute, Utrecht, Netherlands

    • Hans Clevers

Authors

  1. Search for Jarno Drost in:

  2. Search for Hans Clevers in:

Contributions

J.D. and H.C. researched data for the article, wrote the article and reviewed and/or edited the manuscript before submission.

Competing interests

J.D. and H.C. are named as inventors on several patents related to leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)+ stem cell-based organoid technology.

Corresponding author

Correspondence to Jarno Drost.

Glossary

Karyotype

The number and appearance of chromosomes in the nucleus of a cell.

Feeder cells

A layer of cells that is used to support the growth of a cell culture (that is, stem cell cultures) by secretion of important growth factors into the culture medium.

Matrigel

A mouse-derived ex vivo basement membrane substitute that is used to support 3D growth of organoid cultures.

Intraepithelial lymphocytes

(IELs). Lymphocytes residing in the epithelial layer of mammalian mucosal linings, such as the small and large intestines, lungs, upper respiratory tract, reproductive tract and skin.

Mutation signatures

Unique combinations of mutation types caused by different mutational processes.

Base excision repair

A DNA repair mechanism that removes damaged bases (oxidized, alkylated or deaminated) that could otherwise cause mutations.

Caecum

A pouch located between the small and large intestine that is considered to be the beginning of the large intestine and is thus part of the gastrointestinal tract.

Anoikis

A process of programmed cell death initiated by loss of cell–matrix interactions in anchorage-dependent cells.

Serrated colon adenomas

A precursor colorectal cancer (CRC) subtype that is characterized by a serrated histopathological morphology. Serrated CRCs are genetically distinct from the classical adenocarcinomas. Whereas classical adenocarcinomas are typically initiated by mutations in the WNT pathway (for example, adenomatous polyposis coli (APC)), serrated CRCs are likely initiated by BRAF mutations.

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https://doi.org/10.1038/s41568-018-0007-6