Skip to main content

Advertisement

SpringerLink
Log in

Utilizing Patient-Derived Organoids in the Management of Colorectal Cancer with Peritoneal Metastases: A Review of Current Literature

  • Review
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Introduction

Treatment of colorectal cancer-derived peritoneal carcinomatosis (CRC-PC) is challenging due to cellular heterogeneity that exhibits variable degrees of resistance to systemic as well as intraperitoneal chemotherapy. Therefore, it is not a surprise that the majority of patients undergoing cytoreductive surgery with HIPEC will experience recurrence. Patient-derived tumor organoids (PTOs) may be potentially capable of informing clinical treatment decisions at the level of the individual patient. In this study, we review the current landscape of CRC-PC PTO literature.

Methods

PubMed was queried for peer-reviewed publications studying CRC-PC organoids. Original articles which harnessed organoids as a research platform to study CRC-PC were included for review. Xenograft organoid studies were excluded.

Results

A total of 5 articles met inclusion criteria published between 2017 and 2022 and underwent complete analysis. Study topics included optimization of current therapies, identification of novel drug applications, and identification of disease mechanisms. Current therapies studied included systemic chemotherapy, targeted inhibitors, and HIPEC regimens.

Conclusions

Patient-derived tumor organoids are a valuable personalized research tool that can complement real-time clinical settings. Additional research is needed to optimize methodologies of organoid incorporation in patients with colorectal cancer with peritoneal carcinomatosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Siegel RL, et al. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.

    Article  PubMed  Google Scholar 

  2. U.S. Cancer Statistics Working Group. U.S. Department of Health and Human Services, C.f.D.C.a.P.a.N.C.I. U.S. cancer statistics data visualizations tool, based on 2021 submission data (1999–2019). 1999–2019 [cited 2022 November 6, 2022]. Available from: www.cdc.gov/cancer/dataviz.

  3. Siegel RL, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145–64.

    Article  PubMed  Google Scholar 

  4. Jayne DG, et al. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89(12):1545–50.

    Article  CAS  PubMed  Google Scholar 

  5. Colucci G, et al. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol. 2005;23(22):4866–75.

    Article  CAS  PubMed  Google Scholar 

  6. Goodwin RA, Asmis TR. Overview of systemic therapy for colorectal cancer. Clin Colon Rectal Surg. 2009;22(4):251–6.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sugarbaker PH, et al. Neoadjuvant FOLFOX chemotherapy in 34 consecutive patients with mucinous peritoneal carcinomatosis of appendiceal origin. J Surg Oncol. 2010;102(6):576–81.

    Article  PubMed  Google Scholar 

  8. Leung V, et al. Oxaliplatin versus mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis. Eur J Surg Oncol. 2017;43(1):144–9.

    Article  CAS  PubMed  Google Scholar 

  9. Alzahrani NA, et al. Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: a multi-institutional experience. J Surg Oncol. 2019;119(3):336–46.

    Article  CAS  PubMed  Google Scholar 

  10. Verwaal VJ, et al. Recurrences after peritoneal carcinomatosis of colorectal origin treated by cytoreduction and hyperthermic intraperitoneal chemotherapy: location, treatment, and outcome. Ann Surg Oncol. 2004;11(4):375–9.

    Article  PubMed  Google Scholar 

  11. van Oudheusden TR, et al. Incidence and treatment of recurrent disease after cytoreductive surgery and intraperitoneal chemotherapy for peritoneally metastasized colorectal cancer: a systematic review. Eur J Surg Oncol. 2015;41(10):1269–77.

    Article  PubMed  Google Scholar 

  12. Ogunwobi OO, Mahmood F, Akingboye A. Biomarkers in Colorectal Cancer: Current Research and Future Prospects. Int J Mol Sci. 2020;21(15).

  13. de Reynies A, et al. KRAS mutation signature in colorectal tumors significantly overlaps with the cetuximab response signature. J Clin Oncol. 2008;26(13):2228–30; author reply 2230–1.

  14. Van Cutsem E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408–17.

    Article  PubMed  Google Scholar 

  15. Pietrantonio F, et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer. 2015;51(5):587–94.

    Article  CAS  PubMed  Google Scholar 

  16. Rowland A, et al. Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. Br J Cancer. 2015;112(12):1888–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Middha S, et al. Reliable pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data. JCO Precis Oncol. 2017.

  18. Hause RJ, et al. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med. 2016;22(11):1342–50.

    Article  CAS  PubMed  Google Scholar 

  19. Wensink GE, et al. Patient-derived organoids as a predictive biomarker for treatment response in cancer patients. NPJ Precis Oncol. 2021;5(1):30.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer. 2018;18(7):407–18.

    Article  CAS  PubMed  Google Scholar 

  21. Votanopoulos KI, et al. Model of patient-specific immune-enhanced organoids for immunotherapy screening: feasibility study. Ann Surg Oncol. 2020;27(6):1956–67.

    Article  PubMed  Google Scholar 

  22. Ooft SN, et al. Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients. Sci Transl Med. 2019;11(513).

  23. Tiriac H, et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov. 2018;8(9):1112–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nagle PW, et al. Patient-derived tumor organoids for prediction of cancer treatment response. Semin Cancer Biol. 2018;53:258–64.

    Article  CAS  PubMed  Google Scholar 

  25. Laoukili J, et al. Peritoneal metastases from colorectal cancer belong to consensus molecular subtype 4 and are sensitised to oxaliplatin by inhibiting reducing capacity. Br J Cancer. 2022;126(12):1824–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Forsythe SD, et al. Personalized identification of optimal HIPEC perfusion protocol in patient-derived tumor organoid platform. Ann Surg Oncol. 2020;27(13):4950–60.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Forsythe S, et al. Development of a colorectal cancer 3D micro-tumor construct platform from cell lines and patient tumor biospecimens for standard-of-care and experimental drug screening. Ann Biomed Eng. 2020;48(3):940–52.

    Article  PubMed  Google Scholar 

  28. Quenet F, et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):256–66.

    Article  CAS  PubMed  Google Scholar 

  29. Narasimhan V, et al. Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases to direct personalized therapy. Clin Cancer Res. 2020;26(14):3662–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ubink I, et al. Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy. Br J Surg. 2019;106(10):1404–14.

    Article  CAS  PubMed  Google Scholar 

  31. Bozzi F, et al. MIF/CD74 axis is a target for novel therapies in colon carcinomatosis. J Exp Clin Cancer Res. 2017;36(1):16.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Guinney J, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Song N, et al. Clinical outcome from oxaliplatin treatment in stage II/III colon cancer according to intrinsic subtypes: secondary analysis of NSABP C-07/NRG oncology randomized clinical trial. JAMA Oncol. 2016;2(9):1162–9.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Linnekamp JF, et al. Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models. Cell Death Differ. 2018;25(3):616–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Moaven O, et al. Clinical implications of genetic signatures in appendiceal cancer patients with incomplete cytoreduction/HIPEC. Ann Surg Oncol. 2020;27(13):5016–23.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Garland-Kledzik M, et al. Prognostic impact and utility of immunoprofiling in the selection of patients with colorectal peritoneal carcinomatosis for cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). J Gastrointest Surg. 2021;25(1):233–40.

    Article  PubMed  Google Scholar 

  37. Sylvester BE, Vakiani E. Tumor evolution and intratumor heterogeneity in colorectal carcinoma: insights from comparative genomic profiling of primary tumors and matched metastases. J Gastrointest Oncol. 2015;6(6):668–75.

    PubMed  PubMed Central  Google Scholar 

  38. Santini D, et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist. 2008;13(12):1270–5.

    Article  CAS  PubMed  Google Scholar 

  39. Bruun J, et al. Patient-derived organoids from multiple colorectal cancer liver metastases reveal moderate intra-patient pharmacotranscriptomic heterogeneity. Clin Cancer Res. 2020;26(15):4107–19.

    Article  CAS  PubMed  Google Scholar 

  40. Forsythe S, et al. Patient specific sarcoma organoids for personalized translational research: unification of the operating room with rare cancer research and clinical implications. Ann Surg Oncol. 2022.

  41. Orkin RW, et al. A murine tumor producing a matrix of basement membrane. J Exp Med. 1977;145(1):204–20.

    Article  CAS  PubMed  Google Scholar 

  42. Kleinman HK, Martin GR. Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol. 2005;15(5):378–86.

    Article  CAS  PubMed  Google Scholar 

  43. Corning. Corning® Matrigel® basement membrane matrix. 2022. Available from: https://certs-ecatalog.corning.com/life-sciences/product-descriptions/354230.pdf.

  44. Polykandriotis E, et al. To Matrigel or not to Matrigel. Am J Pathol 2008;172(5):1441; author reply 1441–2.

  45. Cruz-Acuna R, Garcia AJ. Synthetic hydrogels mimicking basement membrane matrices to promote cell-matrix interactions. Matrix Biol. 2017;57–58:324–33.

    Article  PubMed  Google Scholar 

  46. Aisenbrey EA, Murphy WL. Synthetic alternatives to Matrigel. Nat Rev Mater. 2020;5(7):539–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mazzocchi A, et al. Optimization of collagen type I-hyaluronan hybrid bioink for 3D bioprinted liver microenvironments. Biofabrication. 2018;11(1): 015003.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Skardal A, et al. A reductionist metastasis-on-a-chip platform for in vitro tumor progression modeling and drug screening. Biotechnol Bioeng. 2016;113(9):2020–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Forsythe SD, et al. Organoid platform in preclinical investigation of personalized immunotherapy efficacy in appendiceal cancer: feasibility study. Clin Cancer Res. 2021;27(18):5141–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Thalheim T, et al. Epigenetic drifts during long-term intestinal organoid culture. Cells. 2021;10(7).

  51. Valenzuela CD, et al. Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for cancers with peritoneal metastasis: a 30-year institutional experience. Ann Surg Oncol. 2022;29(6):3436–45.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Sachs N, et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell. 2018;172(1–2):373–386 e10.

  53. Seppala TT, et al. Patient-derived organoid pharmacotyping is a clinically tractable strategy for precision medicine in pancreatic cancer. Ann Surg. 2020;272(3):427–35.

    Article  PubMed  Google Scholar 

  54. Vlachogiannis G, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018;359(6378):920–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 3D PC-TG. CellTiter-Glo® 3D cell viability assay. 2022; Available from: https://www.promega.com/products/cell-health-assays/cell-viability-and-cytotoxicity-assays/celltiter-glo-3d-cell-viability-assay/?catNum=G9681.

  56. Hammond WA, Swaika A, Mody K. Pharmacologic resistance in colorectal cancer: a review. Ther Adv Med Oncol. 2016;8(1):57–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wake Forest Organoid Research Center (WFORCE), Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Richard A. Erali, Steven D. Forsythe, Cecilia R. Schaaf, Nadeem Wajih, Shay Soker & Konstantinos I. Votanopoulos

  2. Wake Forest Institute of Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Richard A. Erali, Steven D. Forsythe, Cecilia R. Schaaf, Nadeem Wajih, Shay Soker & Konstantinos I. Votanopoulos

  3. Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Steven D. Forsythe, Daniel J. Gironda, Shay Soker & Konstantinos I. Votanopoulos

  4. Department of Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Cecilia R. Schaaf

  5. Division of Surgical Oncology, Department of Surgery, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Richard A. Erali & Konstantinos I. Votanopoulos

Authors
  1. Richard A. Erali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven D. Forsythe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel J. Gironda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cecilia R. Schaaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nadeem Wajih
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shay Soker
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Konstantinos I. Votanopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, article reviews and analysis were performed by Richard Erali and Steven Forsythe. The first draft of the manuscript was written by Richard Erali and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Konstantinos I. Votanopoulos.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erali, R.A., Forsythe, S.D., Gironda, D.J. et al. Utilizing Patient-Derived Organoids in the Management of Colorectal Cancer with Peritoneal Metastases: A Review of Current Literature. J Gastrointest Canc 54, 712–719 (2023). https://doi.org/10.1007/s12029-022-00891-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-022-00891-3

Keywords

Search

Navigation