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      New insights about organoids as model of study for breast cancer research Translated title: Nuevas perspectivas sobre organoides como modelo de estudio para investigación en cáncer de mama

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          Abstract

          Abstract Although the current advances in breast cancer (BC) research, it is still one of the leading causes of death from neoplastic diseases in women and causes millions of new cases worldwide. It has become evident that traditional methods used for BC research have serious limitations. We have reviewed the most recent findings in the application of Breast Cancer Organoids (BCOs) to explore extremely rare BC forms, BC hallmarks, biobanks, and interaction with the microenvironment. Moreover, we explored the importance of its applicability in clinical trials, drug screening, and personalized medicine.

          Translated abstract

          Resumen A pesar de los avances actuales en la investigación del cáncer de mama (CM), sigue siendo una de las principales causas de muerte por enfermedades neoplásicas en mujeres y provoca millones de casos nuevos en todo el mundo. Se ha hecho evidente que los métodos tradicionales utilizados para la investigación en CM tienen serias limitaciones. Hemos revisado los hallazgos más recientes en la aplicación de organoides de cáncer de mama (OCM) para explorar formas extremadamente raras de CM, características distintivas de CM, biobancos e interacción con el microambiente. Además, exploramos la importancia de su aplicabilidad en ensayos clínicos, cribado de fármacos y medicina personalizada.

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          Most cited references68

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.

            The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5(+) stem cells at the bottoms of small-intestinal crypts. Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr5(+) stem cells can also initiate these cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.
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              Prospective derivation of a living organoid biobank of colorectal cancer patients.

              In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely recapitulate several properties of the original tumor. The spectrum of genetic changes within the "living biobank" agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design. PAPERCLIP.
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                Author and article information

                Journal
                gamo
                Gaceta mexicana de oncología
                Gac. mex. oncol.
                Sociedad Mexicana de Oncología A.C. (Ciudad de México, Ciudad de México, Mexico )
                1665-9201
                2565-005X
                December 2022
                : 21
                : 4
                : 135-142
                Affiliations
                [1] Tampico orgnameUniversidad Autónoma de Tamaulipas orgdiv2Dr. Alberto Romo Caballero´s School of Medicine Mexico
                Article
                S2565-005X2022000400135 S2565-005X(22)02100400135
                10.24875/j.gamo.22000110
                ce0e9f40-9bbd-4dbc-b9ee-41f2c5fd5176

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 21 September 2022
                : 18 August 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 68, Pages: 8
                Product

                SciELO Mexico

                Categories
                Review articles

                Organoids,Breast cancer,Clinical trials,Personalized medicine,Organoides,Cáncer de mama,Ensayos clínicos,Medicina personalizada

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