Features of obtaining and prospects for the use of colorectal tumor organoids

Abstract

The review summarizes innovative advances in the field of organoids as a tool for accurate cancer modeling. The conditions for reproducing the microenvironment in vitro based on organoid technology are generalized, various methods for cultivating the tumoroids are considered, and an analysis of their properties is carried out on the example of colorectal cancer.

The final part of the review summarizes the literature data on the use of tumoroids in predicting the therapeutic response of a tumor to chemotherapeutic drugs, studying the mechanisms associated with resistance, and optimizing strategies and potential treatments for patients with malignant tumors. Currently, the tumoroid model is widely used in personalized medicine, basic research, screening of antitumor drugs, and to create libraries of tumors with various mutational profiles.

Keywords

tumor organoid / tumoroid / colorectal cancer / 3D culture

References

[1] Sagaert X, Vanstapel A, Verbeek S. Tumor heterogeneity in colorectal cancer: what do we know so far? Pathobiology. 2018;85(1–2):72–84. doi: 10.1159/000486721

[2] Sagaert X., Vanstapel A., Verbeek S. Tumor heterogeneity in colorectal cancer: what do we know so far? // Pathobiology. 2018. Vol. 85, N 1–2. P. 72–84. doi: 10.1159/000486721

[3] Kaprin AD, Starinskij VV, Shohzadova OA. Sostojanie onkologicheskoj pomoshhi naseleniju Rossii v 2020 godu. 2021. 236 p. (In Russ).

[4] Каприн А.Д., Старинский В.В., Шохзадова О.А. Состояние онкологической помощи населению России в 2020 году. 2021. 236 с.

[5] Weitz J, Koch M, Debus J, et al. Colorectal cancer. Lancet. 2005;365(9454):153–165. doi: 10.1016/S0140-6736(05)17706-X

[6] Weitz J., Koch M., Debus J., et al. Colorectal cancer // Lancet. 2005. Vol. 365, N 9454. P. 153–165. doi: 10.1016/S0140-6736(05)17706-X

[7] Grady WM. Genetic testing for high-risk colon cancer patients. Gastroenterology. 2003;124(6):1574–1594. doi: 10.1016/s0016-5085(03)00376-7

[8] Grady W.M. Genetic testing for high-risk colon cancer patients // Gastroenterology. 2003. Vol. 124, N 6. P. 1574–1594. doi: 10.1016/s0016-5085(03)00376-7

[9] Vilar E., Gruber S.B. Microsatellite instability in colorectal cancer — the stable evidence. Nature Rev Clin Oncol. 2012;7(3):153–162. doi: 10.1038/nrclinonc.2009.237

[10] Vilar E., Gruber S.B. Microsatellite instability in colorectal cancer — the stable evidence // Nature Rev Clin Oncol. 2012. Vol. 7, N 3. P. 153–162. doi: 10.1038/nrclinonc.2009.237

[11] Truninger K, Menigatti M, Luz J, et al. Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Gastroenterol. 2005;128(5):1160–1171. doi: 10.1053/j.gastro.2005.01.056

[12] Truninger K., Menigatti M., Luz J., et al. Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer // Gastroenterol. 2005. Vol. 128, N 5. P. 1160–1171. doi: 10.1053/j.gastro.2005.01.056

[13] Sieber OM, Lipton L, Crabtree M, et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. New Engl J Med. 2003;348(9):791–799. doi: 10.1056/NEJMoa025283

[14] Sieber O.M., Lipton L., Crabtree M., et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH // New Engl J Med. 2003. Vol. 348, N 9. P. 791–799. doi: 10.1056/NEJMoa025283

[15] Bogaert J, Prenen H. Molecular genetics of colorectal cancer. Ann Gastroenterol. 2014;27(1):9–14.

[16] Bogaert J., Prenen H. Molecular genetics of colorectal cancer // Ann Gastroenterol. 2014. Vol. 27, N 1. P. 9–14.

[17] Mudassar S, Khan MS, Khan NP, et al. Possible role of proto-oncogenes in colorectal cancer — a population based study. In: Khan J, editor. Colorectal cancer: surgery, diagnostics and treatment. InTech; 2014. P. 332–361.

[18] Mudassar S., Khan M.S., Khan N.P., et al. Possible role of proto-oncogenes in colorectal cancer — a population based study. In: Khan J., editor. Colorectal cancer: surgery, diagnostics and treatment. InTech; 2014. P. 332–361.

[19] Cercek A, Dos Santos Fernandes G, Roxburgh CS, et al. Mismatch repair-deficient rectal cancer and resistance to neoadjuvant chemotherapy. Clin Cancer Res. 2020:26(13):3271–3279. doi: 10.1158/1078-0432.CCR-19-3728

[20] Cercek A., Dos Santos Fernandes G., Roxburgh C.S., et al. Mismatch repair-deficient rectal cancer and resistance to neoadjuvant chemotherapy // Clin Cancer Res. 2020. Vol. 26, N 13. P. 3271–3279. doi: 10.1158/1078-0432.CCR-19-3728

[21] Benson AB, Venook AP, Cederquist L, et al. Colon cancer, version 1.2017, NCCN Clinical Practice Guidelines in Oncology. J Nat Comprehensive Cancer Net. 2017;15(3):370–398. doi: https://doi.org/10.6004/jnccn.2017.0036

[22] Benson A.B., Venook A.P., Cederquist L., et al. Colon cancer, version 1.2017, NCCN Clinical Practice Guidelines in Oncology // J Nat Comprehensive Cancer Net. 2017. Vol. 15, N 3. P. 370–398. doi: 10.6004/jnccn.2017.0036

[23] Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–1474. doi: 10.1245/s10434-010-0985-4

[24] Edge S.B., Compton C.C. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM // Ann Surg Oncol. 2010. Vol. 17, N 6. P. 1471–1474. doi: 10.1245/s10434-010-0985-4

[25] Mármol I, Sánchez-de-Diego C, Dieste AP, et al. Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci. 2017;18(1):197. doi: 10.3390/ijms18010197

[26] Mármol I., Sánchez-de-Diego C., Pradilla Dieste A., et al. Colorectal carcinoma: a general overview and future perspectives in colorectal cancer // Int J Mol Sci. 2017. Vol. 18, N 1. P. 197. doi: 10.3390/ijms18010197

[27] Amelina EL, Efremova AS, Melyanovskaya YL, et al. Functional tests for assessment of residual CFTR channel activity and personalized selection of efficacious CFTR-modulators for cystic fibrosis patients with ‘mild’ and ‘severe’ genetic variants. Pulmonologiya. 2021;31(2):167–177. (In Russ). doi: 10.18093/0869-0189-2021-31-2-167-177

[28] Амелина Е.Л., Ефремова А.С., Мельяновская Ю.Л., и др. Использование функциональных тестов для оценки остаточной активности канала CFTR и индивидуального подбора эффективных CFTR-модуляторов для лечения пациентов с муковисцидозом с «мягким» и «тяжелым» генетическими вариантами // Пульмонология. 2021. Т. 31, № 2. С. 167–177. doi: 10.18093/0869-0189-2021-31-2-167-177

[29] Holtfreter J. A study of the mechanics of gastrulation. Exp Zool. 1944;95(2):171–212. doi.org/10.1002/jez.1400950203

[30] Holtfreter J. A study of the mechanics of gastrulation // Exp Zool. 1944. Vol. 95, N 2. P. 171–212. doi.org/10.1002/jez.1400950203

[31] Lee GY, Kenny PA, Lee EH, Bissell MJ. Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Methods. 2007;4(4):359–365. doi: 10.1038/nmeth1015

[32] Lee G.Y., Kenny P.A., Lee E.H., Bissell M.J. Three-dimensional culture models of normal and malignant breast epithelial cells // Nat Methods. 2007. Vol. 4, N 4. P. 359–365. doi: 10.1038/nmeth1015

[33] De Angelis ML, Bruselles A, Francescangeli F, et al. Colorectal cancer spheroid biobanks: multi-level approaches to drug sensitivity studies. Cell Biol Tox. 2018;34(6):459–469. doi: 10.1007/s10565-018-9423-3

[34] De Angelis M.L., Bruselles A., Francescangeli F., et al. Colorectal cancer spheroid biobanks: multi-level approaches to drug sensitivity studies // Cell Biol Tox. 2018. Vol. 34, N 6. P. 459–469. doi: 10.1007/s10565-018-9423-3

[35] Aijian AP, Garrell RL. Digital microfluidics for automated hanging drop cell spheroid culture. J Lab Autom. 2015;20(3):283–295. doi: 10.1177/2211068214562002

[36] Aijian A.P., Garrell R.L. Digital microfluidics for automated hanging drop cell spheroid culture // J Lab Autom. 2015. Vol. 20, N 3. P. 283–295. doi: 10.1177/2211068214562002

[37] Lucendo-Villari B, Meseguer-Ripolles J, Drew J, et al. Development of a cost-effective automated platform to produce human liver spheroids for basic and applied research. Biofabrication. 2020;13(1). doi: 10.1088/1758-5090/abbdb2

[38] Lucendo-Villari B., Meseguer-Ripolles J., Drew J., et al. Development of a cost-effective automated platform to produce human liver spheroids for basic and applied research // Biofabrication. 2020. Vol. 13, N 1. doi: 10.1088/1758-5090/abbdb2

[39] Tanner K, Gottesman MM. Beyond 3D culture models of cancer. Sci Transl Med. 2015;7(283):283ps9. doi: 10.1126/scitranslmed.3009367

[40] Tanner K., Gottesman M.M. Beyond 3D culture models of cancer // Sci Transl Med. 2015. Vol. 7, N 283. P. 283ps9. doi: 10.1126/scitranslmed.3009367

[41] Mollica PA, Booth-Creech EN, Reid JA, et al. 3D bioprinted mammary organoids and tumoroids in human mammary derived ECM hydrogels. Acta Biomater. 2019;95:201–213. doi: 10.1016/j.actbio.2019.06.017

[42] Mollica P.A., Booth-Creech E.N., Reid J.A., et al. 3D bioprinted mammary organoids and tumoroids in human mammary derived ECM hydrogels // Acta Biomater. 2019. Vol. 95. P. 201–213. doi: 10.1016/j.actbio.2019.06.017

[43] Bonnesœur S, Morin-Grognet S, Thoumire O, et al. Hyaluronan-based hydrogels as versatile tumor-like models: tunable ECM and stiffness with genipin-crosslinking. J Biomed Mater Res. 2020;108(5):1256–1268. doi: 10.1002/jbm.a.36899

[44] Bonnesœur S., Morin-Grognet S., Thoumire O., et al. Hyaluronan-based hydrogels as versatile tumor-like models: tunable ECM and stiffness with genipin-crosslinking // J Biomed Mater Res. 2020. Vol. 108, N 5. P. 1256–1268. doi: 10.1002/jbm.a.36899

[45] Yang Z, Xu H, Zhao X. Designer self-assembling peptide hydrogels to engineer 3D cell microenvironments for cell constructs formation and precise oncology remodeling in ovarian cancer. Adv Sci (Weinh). 2020;7(9):1903718. doi: 10.1002/advs.201903718

[46] Yang Z., Xu H., Zhao X. Designer self-assembling peptide hydrogels to engineer 3D cell microenvironments for cell constructs formation and precise oncology remodeling in ovarian cancer // Adv Sci (Weinh). 2020. Vol. 7, N 9. P. 1903718. doi: 10.1002/advs.201903718

[47] Benton G, George J, Kleinman H, Arnaoutova IP. Advancing science and technology via 3D culture on basement membrane matrix. J Cell Physiol. 2009;221(1):18–25. doi: 10.1002/jcp.21832

[48] Benton G., George J., Kleinman H., Arnaoutova I.P. Advancing science and technology via 3D culture on basement membrane matrix // J Cell Physiol. 2009. Vol. 221, N 1. P. 18–25. doi: 10.1002/jcp.21832

[49] Kibbey MC. Maintenance of the EHS sarcoma and Matrigel preparation. J Tissue Cult Met. 1994;16:227–230. doi: 10.1007/BF01540656

[50] Kibbey M.C. Maintenance of the EHS sarcoma and Matrigel preparation // J Tissue Cult Met. 1994. Vol. 16. P. 227–230. doi: 10.1007/BF01540656

[51] Albini A, Noonan DM. The “chemoinvasion” assay, 25 years and still going strong: the use of reconstituted basement membranes to study cell invasion and angiogenesis. Curr Opin Cell Biol. 2010;22(5):677–689. doi: 10.1016/j.ceb.2010.08.017

[52] Albini A., Noonan D.M. The “chemoinvasion” assay, 25 years and still going strong: the use of reconstituted basement membranes to study cell invasion and angiogenesis // Curr Opin Cell Biol. 2010. Vol. 22, N 5. P. 677–689. doi: 10.1016/j.ceb.2010.08.017

[53] Benton G, Kleinman H, George J, Arnaoutova I. Multiple uses of basement membrane-like matrix (BME/Matrigel) in vitro and in vivo with cancer cells. Int J Cancer. 2011;128(8):1751–1757. doi: 10.1002/ijc.25781

[54] Benton G., Kleinman H., George J., Arnaoutova I. Multiple uses of basement membrane-like matrix (BME/Matrigel) in vitro and in vivo with cancer cells // Int J Cancer. 2011. Vol. 128, N 8. P. 1751–1757. doi: 10.1002/ijc.25781

[55] Benton G, Arnaoutova I, George J, et al. Matrigel: from discovery and ECM mimicry to assays and models for cancer research. Adv Drug Del Rev. 2014;79-80:3–18. doi: 10.1016/j.addr.2014.06.005

[56] Benton G., Arnaoutova I., George J., et al. Matrigel: from discovery and ECM mimicry to assays and models for cancer research // Adv Drug Deliv Rev. 2014. Vol. 79-80. P. 3–18. doi: 10.1016/j.addr.2014.06.005

[57] Ong C, Yesantharao P, Huang C, et al. 3D bioprinting using stem cells. Pediatr Res. 2018;83(1–2):223–231. doi: 10.1038/pr.2017.252

[58] Ong C.S., Yesantharao P., Huang C.Y., et al. 3D bioprinting using stem cells // Pediatr Res. 2018. Vol. 83, N 1-2. P. 223–231. doi: 10.1038/pr.2017.252

[59] Matai I, Kaur G, Seyedsalehi A, et al. Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials. 2020;226:119536. doi: 10.1016/j.biomaterials.2019.119536

[60] Matai I., Kaur G., Seyedsalehi A., et al. Progress in 3D bioprinting technology for tissue/organ regenerative engineering // Biomaterials. 2020. Vol. 226. P. 119536. doi: 10.1016/j.biomaterials.2019.119536

[61] Tam RY, Smith LJ, Shoichet MS. Engineering cellular microenvironments with photo- and enzymatically responsive hydrogels: toward biomimetic 3D cell. Acc Chem Res. 2018;50(4):703–713. doi: 10.1021/acs.accounts.6b00543

[62] Tam R.Y., Smith L.J., Shoichet M.S. Engineering cellular microenvironments with photo- and enzymatically responsive hydrogels: toward biomimetic 3D cell // Acc Chem Res. 2018. Vol. 50, N 4. P. 703–713. doi: 10.1021/acs.accounts.6b00543

[63] Arya N, Sardana V, Saxena M, et al. Recapitulating tumour microenvironment in chitosan-gelatin three-dimensional scaffolds: an improved in vitro tumour model. J R Soc Interface. 2012;9(77):3288–3302. doi: 10.1098/rsif.2012.0564

[64] Arya N., Sardana V., Saxena M., et al. Recapitulating tumour microenvironment in chitosan-gelatin three-dimensional scaffolds: an improved in vitro tumour model // J R Soc Interface. 2012. Vol. 9, N 77. P. 3288–3302. doi: 10.1098/rsif.2012.0564

[65] Mandrycky C, Wang Z, Kim K, Kim DH. 3D bioprinting for engineering complex tissues. Biotech Adv. 2016;34(4):422–434. doi: 10.1016/j.biotechadv.2015.12.011

[66] Mandrycky C., Wang Z., Kim K., Kim D.H. 3D bioprinting for engineering complex tissues // Biotech Adv. 2016. Vol. 34, N 4. P. 422–434. doi: 10.1016/j.biotechadv.2015.12.011

[67] Miller JS, Stevens KR, Yang MT, et al. Rapid casting of patterned vascular networks for perfusable engineered 3D tissues. Nat Mater. 2012;11(9):768–774. doi: 10.1038/nmat3357

[68] Miller J.S., Stevens K.R., Yang M.T., et al. Rapid casting of patterned vascular networks for perfusable engineered 3D tissues // Nat Mater. 2012. Vol. 11, N 9. P. 768–774. doi: 10.1038/nmat3357

[69] Wang MO, Piard CM, Melchiorri A, et al. Evaluating changes in structure and cytotoxicity during in vitro degradation of three-dimensional printed scaffolds. Tissue Eng Part A. 2015;21(9-10):1642–1653. doi: 10.1089/ten.TEA.2014.0495

[70] Wang M.O., Piard C.M., Melchiorri A., et al. Evaluating changes in structure and cytotoxicity during in vitro degradation of three-dimensional printed scaffolds // Tissue Eng Part A. 2015. Vol. 21, N 9-10. P. 1642–1653. doi: 10.1089/ten.TEA.2014.0495

[71] Lee JS, Hong JM, Jung JW, et al. 3D printing of composite tissue with complex shape applied to ear regeneration. Biofabrication. 2014;6(2):024103. doi: 10.1088/1758-5082/6/2/024103

[72] Lee J.S., Hong J.M., Jung J.W., et al. 3D printing of composite tissue with complex shape applied to ear regeneration // Biofabrication. 2014. Vol. 6, N 2. P. 024103. doi: 10.1088/1758-5082/6/2/024103

[73] Urkasemsin G, Rungarunlert S, Ferreira JN. 3D bioprinting: what does the future hold? Methods Mol Biol. 2020;2140:243–249. doi: 10.1007/978-1-0716-0520-2_16

[74] Urkasemsin G., Rungarunlert S., Ferreira J.N. 3D bioprinting: what does the future hold? // Methods Mol Biol. 2020. Vol. 2140. P. 243–249. doi: 10.1007/978-1-0716-0520-2_16

[75] Dey M, Ozbolat I. 3D bioprinting of cells, tissues and organs. Sci Rep. 2020;10(1):14023. doi: 10.1038/s41598-020-70086-y

[76] Dey M., Ozbolat I. 3D bioprinting of cells, tissues and organs // Sci Rep. 2020. Vol. 10, N 1. C. 14023. doi: 10.1038/s41598-020-70086-y

[77] Qin X, Sufi J, Vlckova P, et al. Cell-type-specific signaling networks in heterocellular organoids. Nat Methods. 2020;17(3):335–342. doi: 10.1038/s41592-020-0737-8

[78] Qin X., Sufi J., Vlckova P., et al. Cell-type-specific signaling networks in heterocellular organoids // Nat Methods. 2020. Vol. 17, N 3. P. 335–342. doi: 10.1038/s41592-020-0737-8

[79] Schutgens F, Rookmaaker MB, Margaritis T, et al. Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat Biotechnol. 2019;37(3):303–313. doi: 10.1038/s41587-019-0048-8

[80] Schutgens F., Rookmaaker M.B., Margaritis T., et al. Tubuloids derived from human adult kidney and urine for personalized disease modeling // Nat Biotechnol. 2019. Vol. 37, N 3. P. 303–313. doi: 10.1038/s41587-019-0048-8

[81] Zhang B, Korolj A, Lai BFL, Radisic M. Advances in organ-on-a-chip engineering. Nature Rev Mater. 2018;3(8):257–278. doi: 10.1038/s41578-018-0034-7

[82] Zhang B., Korolj A., Lai B.F.L., Radisic M. Advances in organ-on-a-chip engineering // Nature Rev Mater. 2018. Vol. 3, N 8. P. 257–278. doi: 10.1038/s41578-018-0034-7

[83] Campos DF, Marquez AB, O’seanain C, et al. Exploring cancer cell behavior in vitro in three-dimensional multicellular bioprintable collagen-based hydrogels. Cancers (Basel). 2019;11(2):180. doi: 10.3390/cancers11020180

[84] Campos D.F., Marquez A., O’seanain C., et al. Exploring cancer cell behavior in vitro in three-dimensional multicellular bioprintable collagen-based hydrogels // Cancers (Basel). 2019. Vol. 11, N 2. P. 180. doi: 10.3390/cancers11020180

[85] Modi U, Makwana P, Vasita R. Molecular insights of metastasis and cancer progression derived using 3D cancer spheroid co-culture in vitro platform. Crit Rev Oncol Hematol. 2021;168:103511. doi: 10.1016/j.critrevonc.2021.103511

[86] Modi U., Makwana P., Vasita R. Molecular insights of metastasis and cancer progression derived using 3D cancer spheroid co-culture in vitro platform // Crit Rev Oncol Hematol. 2021. Vol. 168. P. 103511. doi: 10.1016/j.critrevonc.2021.103511

[87] Lovitt CJ, Shelper TB, Avery VM. Advanced cell culture techniques for cancer drug discovery. Biology (Basel). 2014;3(2):345–367. doi: 10.3390/biology3020345

[88] Lovitt C.J., Shelper T.B., Avery V.M. Advanced cell culture techniques for cancer drug discovery // Biology (Basel). 2014. Vol. 3, N 2. P. 345–367. doi: 10.3390/biology3020345

[89] Van De Wetering M, Francies HE, Francis JM, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 2015;161(4):933–945. doi: 10.1016/j.cell.2015.03.053

[90] Van De Wetering M., Francies H.E., Francis J.M., et al. Prospective derivation of a living organoid biobank of colorectal cancer patients // Cell. 2015. Vol. 161, N 4. P. 933–945. doi: 10.1016/j.cell.2015.03.053

[91] Lyu X, Xu H, Song Y, et al. Organoid technology and applications in cancer research. J Hematol Oncol. 2018;11(1):116. doi: 10.1186/s13045-018-0662-9

[92] Lyu X., Xu H., Song Y., et al. Organoid technology and applications in cancer research // J Hematol Oncol. 2018. Vol. 11, N 1. P. 116. doi: 10.1186/s13045-018-0662-9

[93] Hughes CS, Postovit LM, Lajoie GA. Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics. 2010;10(9):1886–1890. doi: 10.1002/pmic.200900758

[94] Hughes C.S., Postovit L.M., Lajoie G.A. Matrigel: a complex protein mixture required for optimal growth of cell culture // Proteomics. 2010. Vol. 10, N 9. P. 1886–1890. doi: 10.1002/pmic.200900758

[95] Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018;359(6378):920–926. doi: 10.1126/science.aao2774

[96] Vlachogiannis G., Hedayat S., Vatsiou A., et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers // Science. 2018. Vol. 359. N 6378. P. 920–926. doi: 10.1126/science.aao2774

[97] Tevis KM, Colson YL, Grinstaff MW. Embedded spheroids as models of the cancer microenvironment. Adv Biosyst. 2017;1(10):1700083. doi: 10.1002/adbi.201700083

[98] Tevis K.M., Colson Y.L., Grinstaff M.W. Embedded spheroids as models of the cancer microenvironment // Adv Biosyst. 2017. Vol. 1, N 10. P. 1700083. doi: 10.1002/adbi.201700083

[99] Smyrek I, Mathew B, Fischer SC, et al. E-cadherin, actin, microtubules and FAK dominate different spheroid formation phases and important elements of tissue integrity. Biol Open. 2019;8(1):bio037051. doi: 10.1242/bio.037051

[100] Smyrek I., Mathew B., Fischer S.C., et al. E-cadherin, actin, microtubules and FAK dominate different spheroid formation phases and important elements of tissue integrity // Biol Open. 2019. Vol. 8, N 1. P. bio037051. doi: 10.1242/bio.037051

[101] Pauli C, Hopkins B.D, Prandi D, et al. Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov. 2017;7(5):462–477. doi: 10.1158/2159-8290.CD-16-1154

[102] Pauli C., Hopkins B.D., Prandi D., et al. Personalized in vitro and in vivo cancer models to guide precision medicine // Cancer Discov. 2017. Vol. 7, N 5. P. 462–477. doi: 10.1158/2159-8290.CD-16-1154

[103] Fujii M, Shimokawa M, Date S, et al. Colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell. 2016;18(6):827–838. doi: 10.1016/j.stem.2016.04.003

[104] Fujii M., Shimokawa M., Date S., et al. Colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis // Cell Stem Cell. 2016. Vol. 18, N 6. P. 827–838. doi: 10.1016/j.stem.2016.04.003

[105] Engel RM, Jardé T, Oliva K, et al. Modeling colorectal cancer: a bio-resource of 50 patient-derived organoid lines. J Gastroenterol Hepatol. 2022;37(5):898–907. doi: 10.1111/jgh.15818

[106] Engel R.M., Jardé T., Oliva K., et al. Modeling colorectal cancer: a bio-resource of 50 patient-derived organoid lines // J Gastroenterol Hepatol. 2022. Vol. 37, N 5. P. 898–907. doi: 10.1111/jgh.15818

[107] Bayramov AV, Eroshkin FM, Borodulin AV, et al. Secreted protein noggin4 participates in the formation of forebrain structures in xenopus laevis by inhibiting the Wnt/beta-catenin signaling pathway. Russian Journal of Developmental Biology. 2016;47(4):202–206. (In Russ).

[108] Байрамов А.В., Ерошкин Ф.М., Бородулин А.В., и др. Секретируемый белок Noggin4 участвует в формировании переднеголовных структур шпорцевой лягушки, ингибируя Wnt/beta-catenin сигнальный каскад // Онтогенез. 2016. Т. 47, № 4. С. 229–234. doi: 10.7868/S0475145016040029

[109] Ganesh K, Wu C, O’Rourke KP, et al. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat Med. 2019;25(10):1607–1614. doi: 10.1038/s41591-019-0584-2

[110] Ganesh K., Wu C., O’Rourke K.P., et al. A rectal cancer organoid platform to study individual responses to chemoradiation // Nat Med. 2019. Vol. 25, N 10. P. 1607–1614. doi: 10.1038/s41591-019-0584-2

[111] Bartlett R, Everett W, Lim S, et al. Personalized in vitro cancer modeling — fantasy or reality? Transl Oncol. 2014;7(6):657–664. doi: 10.1016/j.tranon.2014.10.006

[112] Bartlett R., Everett W., Lim S., et al. Personalized in vitro cancer modeling — fantasy or reality? // Transl Oncol. 2014. Vol. 7, N 6. P. 657–664. doi: 10.1016/j.tranon.2014.10.006

[113] Drost J, Van Jaarsveld RH, Ponsioen B, et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature. 2015;521(7550):43–47. doi: 10.1038/nature14415

[114] Drost J., Van Jaarsveld R.H., Ponsioen B., et al. Sequential cancer mutations in cultured human intestinal stem cells // Nature. 2015. Vol. 521. N 7550. P. 43–47. doi: 10.1038/nature14415

[115] Matano M, Date S, Shimokawa M, et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med. 2015;21(3):256–262. doi: 10.1038/nm.3802

[116] Matano M., Date S., Shimokawa M., et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids // Nat Med. 2015. Vol. 21, N 3. P. 256–262. doi: 10.1038/nm.3802

[117] Li H, Rokavec M, Jiang L, et al. Antagonistic effects of p53 and HIF1A on microRNA-34a regulation of PPP1R11 and STAT3 and hypoxia-induced epithelial to mesenchymal transition in colorectal cancer cells. Gastroenterology. 2017;153(2):505–520. doi: 10.1053/j.gastro.2017.04.017

[118] Li H., Rokavec M., Jiang L., et al. Antagonistic effects of p53 and HIF1A on microRNA-34a regulation of PPP1R11 and STAT3 and hypoxia-induced epithelial to mesenchymal transition in colorectal cancer cells // Gastroenterology. 2017. Vol. 153, N 2. P. 505–520. doi: 10.1053/j.gastro.2017.04.017

[119] Gowrikumar S, Primeaux M, Pravoverov K, et al. A claudin-based molecular signature identifies high-risk, chemoresistant colorectal cancer patients. Cells. 2021;10(9):2211. doi: 10.3390/cells10092211

[120] Gowrikumar S., Primeaux M., Pravoverov K., et al. A claudin-based molecular signature identifies high-risk, chemoresistant colorectal cancer patients // Cells. 2021. Vol. 10, N 9. P. 2211. doi: 10.3390/cells10092211

[121] Bishnupuri KS, Alvarado DM, Khouri AN, et al. IDO1 and kynurenine pathway metabolites activate PI3K-Akt signaling in the neoplastic colon epithelium to promote cancer cell proliferation and inhibit apoptosis. Cancer Res. 2019;79(6):1138–1150. doi: 10.1158/0008-5472.CAN-18-0668

[122] Bishnupuri K.S., Alvarado D.M., Khouri A.N., et al. IDO1 and kynurenine pathway metabolites activate PI3K-Akt signaling in the neoplastic colon epithelium to promote cancer cell proliferation and inhibit apoptosis // Cancer Res. 2019. Vol. 79, N 6. P. 1138–1150. doi: 10.1158/0008-5472.CAN-18-0668

[123] Kobayashi H, Gieniec KA, Lannagan TRM, et al. The origin and contribution of cancer-associated fibroblasts in colorectal carcinogenesis. Gastroenterology. 2022;162(3):890–906. doi: 10.1053/j.gastro.2021.11.037

[124] Kobayashi H., Gieniec K.A., Lannagan T.R.M., et al. The origin and contribution of cancer-associated fibroblasts in colorectal carcinogenesis // Gastroenterology. 2022. Vol. 162, N 3. P. 890–906. doi: 10.1053/j.gastro.2021.11.037

[125] Gupta K, Jones JC, Farias VA, et al. Identification of synergistic drug combinations to target KRAS-driven chemoradioresistant cancers utilizing tumoroid models of colorectal adenocarcinoma and recurrent glioblastoma. Front Oncol. 2022;12:840241. doi: 10.3389/fonc.2022.840241

[126] Gupta K., Jones J.C., Farias V.A., et al. Identification of synergistic drug combinations to target KRAS-driven chemoradioresistant cancers utilizing tumoroid models of colorectal adenocarcinoma and recurrent glioblastoma // Front Oncol. 2022. Vol. 12. P. 840241. doi: 10.3389/fonc.2022.840241

[127] Verissimo CS, Overmeer RM, Ponsioen B, et al. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening. Elife. 2016;5:e18489. doi: 10.7554/eLife.18489

[128] Verissimo C.S., Overmeer R.M., Ponsioen B., et al. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening // Elife. 2016. Vol. 5. P. e18489. doi: 10.7554/eLife.18489

[129] Fleming NI, Jorissen RN, Mouradov D, et al. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res. 2013;73(2):725–735. doi: 10.1158/0008-5472.CAN-12-2706

[130] Fleming N.I., Jorissen R.N., Mouradov D., et al. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer // Cancer Res. 2013. Vol. 73, N 2. P. 725–735. doi: 10.1158/0008-5472.CAN-12-2706

[131] Zhao M, Mishra L, Deng CX. The role of TGF-β/SMAD4 signaling in cancer. Int J Biol Sci. 2018;14(2):111–123. doi: 10.7150/ijbs.23230

[132] Zhao M., Mishra L., Deng C.X. The role of TGF-β/SMAD4 signaling in cancer // Int J Biol Sci. 2018. Vol. 14, N 2. P. 111–123. doi: 10.7150/ijbs.23230

[133] Li XL, Zhou J, Chen ZR, et al. P53 mutations in colorectal cancer — molecular pathogenesis and pharmacological reactivation. World J Gastroenterol. 2015;21(1):84–93. doi: 10.3748/wjg.v21.i1.84

[134] Li X.L., Zhou J., Chen Z.R., et al. P53 mutations in colorectal cancer — molecular pathogenesis and pharmacological reactivation // World J Gastroenterol. 2015. Vol. 21, N 1. P. 84–93. doi: 10.3748/wjg.v21.i1.84

[135] Zhao Y, Li Y, Sheng J, et al. P53-R273H mutation enhances colorectal cancer stemness through regulating specific lncRNAs. J Exp Clin Cancer Res. 2019;38(1):379. doi: 10.1186/s13046-019-1375-9

[136] Zhao Y., Li Y., Sheng J., et al. P53-R273H mutation enhances colorectal cancer stemness through regulating specific lncRNAs // J Exp Clin Cancer Res. 2019. Vol. 38, N 1. P. 379. doi: 10.1186/s13046-019-1375-9

[137] Afrăsânie VA, Marinca MV, Alexa-Stratulat T, et al. KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer — practical implications for the clinician. Radiol Oncol. 2019;53(3):265–274. doi: 10.2478/raon-2019-0033

[138] Afrăsânie V.A., Marinca M.V., Alexa-Stratulat T., et al. KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer — practical implications for the clinician // Radiol Oncol. 2019. Vol. 53, N 3. P. 265–274. doi: 10.2478/raon-2019-0033

[139] Paleari L, Puntoni M, Clavarezza M, et al. PIK3CA mutation, aspirin use after diagnosis and survival of colorectal cancer. A systematic review and meta-analysis of epidemiological studies. Clin Oncol (R Coll Radiol). 2016;28(5):317–326. doi: 10.1016/j.clon.2015.11.008

[140] Paleari L., Puntoni M., Clavarezza M., et al. PIK3CA mutation, aspirin use after diagnosis and survival of colorectal cancer. A systematic review and meta-analysis of epidemiological studies // Clin Oncol (R Coll Radiol). 2016. Vol. 28, N 5. P. 317–326. doi: 10.1016/j.clon.2015.11.008

[141] Weeber F, Ooft SN, Dijkstra KK, et al. Tumor organoids as a pre-clinical cancer model for drug discovery. Cell Chem Biol. 2017;24(9):1092–1100. doi: 10.1016/j.chembiol.2017.06.012

[142] Weeber F., Ooft S.N., Dijkstra K.K., et al. Tumor organoids as a pre-clinical cancer model for drug discovery // Cell Chem Biol. 2017. Vol. 24, N 9. P. 1092–1100. doi: 10.1016/j.chembiol.2017.06.012

[143] Jackson DN, Alula KM, Delgado-Deida Y, et al. The synthetic small molecule FL3 combats intestinal tumorigenesis via Axin1-mediated inhibition of Wnt/beta-catenin signaling. Cancer Res. 2020;80(17):3519–3529. doi: 10.1158/0008-5472.CAN-20-0216

[144] Jackson D.N., Alula K.M., Delgado-Deida Y. The synthetic small molecule FL3 combats intestinal tumorigenesis via Axin1-mediated inhibition of Wnt/beta-catenin signaling // Cancer Res. 2020. Vol. 80, N 17. P. 3519–3529. doi: 10.1158/0008-5472.CAN-20-0216

[145] Zhao Y, Wang C, Goel A. Andrographis overcomes 5-fluorouracil-associated chemoresistance through inhibition of DKK1 in colorectal cancer. Carcinogenesis. 2021;42(6):814–825. doi: 10.1093/carcin/bgab027

[146] Zhao Y., Wang C., Goel A. Andrographis overcomes 5-fluorouracil-associated chemoresistance through inhibition of DKK1 in colorectal cancer // Carcinogenesis. 2021. Vol. 42, N 6. P. 814–825. doi: 10.1093/carcin/bgab027

[147] Zhou Z, Cong L, Cong X. Patient-derived organoids in precision medicine: drug screening, organoid-on-a-chip and living organoid biobank. Front Oncol. 2021;11:762184. doi: 10.3389/fonc.2021.762184

[148] Zhou Z., Cong L., Cong X. Patient-derived organoids in precision medicine: drug screening, organoid-on-a-chip and living organoid biobank // Front Oncol. 2021. Vol. 11. P. 762184. doi: 10.3389/fonc.2021.762184

[149] Gong P, Wang H, Zhang J, et al. Telomere maintenance-associated PML is a potential specific therapeutic target of human colorectal cancer. Transl Oncol. 2019;12(9):1164–1176. doi: 10.1016/j.tranon.2019.05.010

[150] Gong P., Wang H., Zhang, J., et al. Telomere maintenance-associated pml is a potential specific therapeutic target of human colorectal cancer // Transl Oncol. 2019. Vol. 12, N 9. P. 1164–1176. doi: 10.1016/j.tranon.2019.05.010

[151] Voest EE, Bernards R. DNA-guided precision medicine for cancer: a case of irrational exuberance? Cancer Discov. 2016;6(2):130–132. doi: 10.1158/2159-8290.CD-15-1321

[152] Voest E.E., Bernards R. DNA-guided precision medicine for cancer: a case of irrational exuberance? // Cancer Discov. 2016. Vol. 6, N 2. P. 130–132. doi: 10.1158/2159-8290.CD-15-1321

[153] Flores-Pérez JA, De La F, Oliva R, et al. Translational research and onco-omics applications in the era of cancer personal genomics. Adv Exp Med Biol. 2019;1168.

[154] Flores-Pérez J.A., De La F., Oliva R., et al. Translational research and onco-omics applications in the era of cancer personal genomics // Adv Exp Med Biol. 2019. 1168.

[155] Drost J, Clevers H. Organoids in cancer research. Nature Rev Cancer. 2018;18(7):407–418. doi: 10.1038/s41568-018-0007-6

[156] Drost J., Clevers H. Organoids in cancer research // Nature Rev Cancer. 2018. Vol. 18, N 7. P. 407–418. doi: 10.1038/s41568-018-0007-6

[157] Liu J, Huang X, Huang L, et al. Organoid: next-generation modeling of cancer research and drug development. Front Oncol. 2022;11:826613. doi: 10.3389/fonc.2021.826613

[158] Liu J., Huang X., Huang L., et al. Organoid: next-generation modeling of cancer research and drug development // Front Oncol. 2022. Vol. 11. P. 826613. doi: 10.3389/fonc.2021.826613

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