Use of Patient-Derived Organoids as a Treatment Selection Model for Colorectal Cancer: A Narrative Review

Furbo, Sara; Urbano, Paulo C. M.; Raskov, Hans; Troelsen, Jesper T.; Fiehn, Anne-Marie Kanstrup; Gögenür, Ismail

doi:10.3390/cancers14041069

Cited by 6 publications

(10 citation statements)

References 66 publications

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“…Patients were then treated with medication based off their organoid's sensitivity results. 68 out of 80 patients had the same response as their organoid counterpart when treatment was complete [18,20].…”

Section: Drug Therapy Testingmentioning

confidence: 87%

“…For patients with stages I-III colorectal cancer, the first course of treatment is resection of the tumor, followed by adjuvant chemotherapy, which usually consists of 5-Flourouracil (5-Fu) and oxaliplatin. Although this approach can be successful short-term, patients have roughly a 40% chance of disease recurrence within 5 years [18].…”

Section: Colorectal Cancermentioning

confidence: 99%

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The Use of Stem Cell-Derived Organoids in Cancer Treatment Research

Gaillicchio¹

2022

JRMBR

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Cancer is one of the leading causes of death worldwide. While some forms of cancer are more manageable and nonfatal with treatments like chemotherapy and radiation, other forms are not as manageable and have high fatality rates, such as colorectal cancer. Colorectal cancer most commonly occurs in elderly adults but has the potential to occur at any age. Due to its sometimes-undetectable symptoms, it is often diagnosed at a very late stage. Once diagnosed, there are different levels of treatment. For example, surgical resection, chemotherapy, radiation, or any combination of the three can occur. When tumors are unresectable, patients are often left with little chance of survival, and receive only the extension of survival for a short period of time. While surgical resection, chemotherapy and radiation have had success in some patients, high recurrence rates and a lack of response to treatments have left patients and researchers looking for new treatments that will result in better survival rates for patients. Researchers have begun to answer the calls for new treatments with the discovery of patient-derived organoids. Patient-derived organoids are harvested from adult stem cells in the desired tissue, or from cancer cells in a patient’s tumor. The cells taken from the patient are then grown ex-vivo in conditions that mimic the inside of the body. Organoids have grown to show both structural and physiological similarities to their parent organ. While organoids have not yet grown to be as large and highly vascularized as their parent organ, they have been useful in disease modeling and drug therapy testing. Patient-derived organoids that have been grown ex-vivo have shown to overlap almost completely with their parent organ in terms of genetic sequence and molecular makeup. Due to their high number of genetic similarities, patient-derived organoids have been shown to react the same way to certain drug treatments in a few studies, which allows researchers to provide combinations of different cancer drug treatments that are tailored to each individual patient, rather than using a standardized approach that only seems to work for some patients. Patient-derived organoids are still a rather new approach to cancer drug therapy testing, and they still present some limitations, such as their inability to grow as large and as highly vascularized as their parent organ. While these limitations may have the ability to hinder the effectiveness of patient-derived organoids, some organoids have shown success in colorectal cancer drug therapy trials, and their limitations are likely to be overcome as more information is known about patient-derived organoids. Organoids are a promising approach to the treatment of colorectal cancer and have the potential to help save more patients than previous approaches.

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Section: Drug Therapy Testingmentioning

confidence: 87%

Section: Colorectal Cancermentioning

confidence: 99%

The Use of Stem Cell-Derived Organoids in Cancer Treatment Research

Gaillicchio¹

2022

JRMBR

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“…On the basis of this model, many laboratories have established PDO from different tumor types to study the cancer biology and in several cases their predictive value in drug sensitivity testing aiming to their use for personalized treatment (14). In line with their original intestinal development, this has been particularly frequent in CRC (7,15). According to the 100% negative predictive value of drug assays in PDO models (16), the lack of effect of oxaliplatin suggested that this drug was not a valid therapeutic option for our patient.…”

Section: Discussionmentioning

confidence: 99%

“…They have the potential to avoid futile treatments and harmful side effects for the patients. Studies addressing the use of organoids to treat patients with CRC are emerging in the literature (7). Patients with CRC peritoneal metastases treated with HIPEC or PIPAC represent a unique subgroup of patients in which tumor specimen from the metastatic site can be sampled during the intervention in order to generate organoids and perform the drug-screening analysis.…”

Section: Introductionmentioning

confidence: 99%

Tailored chemotherapy for colorectal cancer peritoneal metastases based on a drug-screening platform in patient-derived organoids: a case report

Prieto¹,

Barbáchano²,

Rodrı́guez-Salas³

et al. 2023

J Gastrointest Oncol

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Background: Peritoneal metastasis from colorectal cancer (CRC) has limited therapeutic options and poor prognosis. Systemic chemotherapy combined with cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC) have yielded initial promising results. However, standard local therapies with oxaliplatin and mitomycin are not optimal and a better individualized management of these patients remains as an unmet clinical need. Patientderived organoid (PDO) technology allows to culture in three dimensions normal and cancer stem cells (CSC) that self-organize in multicellular structures that recapitulates some of the features of the particular organ or tumor of origin, emerging as a promising tool for drug-testing and precision medicine. This technology could improve the efficacy of systemic and intraperitoneal chemotherapy and avoid unnecessary treatments and side effects to the patient.Case Description: Here we report a case of a 45-year-old man with a rectal adenocarcinoma with liver, lymph node and peritoneal metastases. The patient was treated with systemic chemotherapy (FOLFOXIRI plus Bevacizumab) and was subjected to mitomycin-based PIPAC. We generated patient-derived peritoneal carcinomatosis organoids in order to screen the activity of drugs for a personalized treatment. Both 5-FU and SN-38, the active irinotecan derivative, displayed strong cytotoxicity, while the response to oxaliplatin was much lower. Although the development of a colo-cutaneous fistulae prevented from further PIPAC, the patient continued with fluoropirimidine maintenance treatment based on standard clinical practice and the drug-screening test performed on organoids.Conclusions: Our results suggest that the peritoneal implant shows chemoresistance to oxaliplatin, while it might still be sensitive to irinotecan and 5-FU, which supports a potential benefit of these two drugs in the local and/or systemic treatment of our patient. This study shows the strength of the utility of the establishment of organoids for drug response assays and thus, for the personalized treatment of colorectal carcinomatosis patients.

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“…Assembloids exhibit an even greater level of complexity, as multiple cell types are used to recapture the multitude of tissues of which the target organ is built in vivo [60,61]. PDCO-derived organoids are investigated as potential clinical tools for the personalization of oncological treatment and response prediction [62][63][64]. The merger of 3D-bioprinting and organoid technologies both accelerates organoid formation and increases the potential organoid complexity [65].…”

Section: D-bioprinting Applications In Solid Tumor Microenvironment R...mentioning

confidence: 99%

Perspectives for 3D-Bioprinting in Modeling of Tumor Immune Evasion

Staros

Michalak

Rusinek

et al. 2022

Cancers

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In a living organism, cancer cells function in a specific microenvironment, where they exchange numerous physical and biochemical cues with other cells and the surrounding extracellular matrix (ECM). Immune evasion is a clinically relevant phenomenon, in which cancer cells are able to direct this interchange of signals against the immune effector cells and to generate an immunosuppressive environment favoring their own survival. A proper understanding of this phenomenon is substantial for generating more successful anticancer therapies. However, classical cell culture systems are unable to sufficiently recapture the dynamic nature and complexity of the tumor microenvironment (TME) to be of satisfactory use for comprehensive studies on mechanisms of tumor immune evasion. In turn, 3D-bioprinting is a rapidly evolving manufacture technique, in which it is possible to generate finely detailed structures comprised of multiple cell types and biomaterials serving as ECM-analogues. In this review, we focus on currently used 3D-bioprinting techniques, their applications in the TME research, and potential uses of 3D-bioprinting in modeling of tumor immune evasion and response to immunotherapies.

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Use of Patient-Derived Organoids as a Treatment Selection Model for Colorectal Cancer: A Narrative Review

Cited by 6 publications

References 66 publications

The Use of Stem Cell-Derived Organoids in Cancer Treatment Research

The Use of Stem Cell-Derived Organoids in Cancer Treatment Research

Tailored chemotherapy for colorectal cancer peritoneal metastases based on a drug-screening platform in patient-derived organoids: a case report

Perspectives for 3D-Bioprinting in Modeling of Tumor Immune Evasion

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