ABSTRACT
PURPOSE: Whilst the treatment paradigm for colorectal cancer has evolved significantly over time, there is still a lack of reliable biomarkers of treatment response. Treatment decisions are based on high-risk features such as advanced TNM stage and histology. The role of the tumour microenvironment, which can influence tumour progression and treatment response, has generated considerable interest. Patient-derived explant cultures allow preservation of native tissue architecture and tumour microenvironment. The aim of the scoping review is to evaluate the utility of patient-derived explant cultures as a preclinical model in colorectal cancer. METHODS: A search was conducted using Ovid MEDLINE, EMBASE, Web of Science, and Cochrane databases from start of database records to September 1, 2022. We included all peer-reviewed human studies in English language which used patient-derived explants as a preclinical model in primary colorectal cancer. Eligible studies were grouped into the following categories: assessing model feasibility; exploring tumour microenvironment; assessing ex vivo drug responses; discovering and validating biomarkers. RESULTS: A total of 60 studies were eligible. Fourteen studies demonstrated feasibility of using patient-derived explants as a preclinical model. Ten studies explored the tumour microenvironment. Thirty-eight studies assessed ex vivo drug responses of chemotherapy agents and targeted therapies. Twenty-four studies identified potential biomarkers of treatment response. CONCLUSIONS: Given the preservation of tumour microenvironment and tumour heterogeneity, patient-derived explants has the potential to identify reliable biomarkers, treatment resistance mechanisms, and novel therapeutic agents. Further validation studies are required to characterise, refine and standardise this preclinical model before it can become a part of precision medicine in colorectal cancer.
Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Humans , Precision Medicine , Antineoplastic Agents/therapeutic use , Biomarkers , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Tumor MicroenvironmentSubject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Appendiceal Neoplasms/diagnostic imaging , Appendiceal Neoplasms/surgery , Rectal Neoplasms/diagnostic imaging , Appendiceal Neoplasms/pathology , Colonoscopy/methods , Diagnosis, Differential , Follow-Up Studies , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Positron-Emission Tomography/methods , Rectal Neoplasms/surgery , Treatment OutcomeSubject(s)
Adenocarcinoma/complications , Intestinal Obstruction/therapy , Intestinal Perforation/etiology , Rectal Neoplasms/complications , Stents/adverse effects , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Aged , Colonoscopy/methods , Colostomy/methods , Follow-Up Studies , Humans , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/etiology , Intestinal Perforation/surgery , Male , Neoplasm Invasiveness/pathology , Neoplasm Staging , Palliative Care/methods , Peritonitis/etiology , Peritonitis/physiopathology , Peritonitis/therapy , Positron-Emission Tomography/methods , Proctectomy/methods , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/surgery , Risk AssessmentABSTRACT
Pleomorphic xanthoastrocytoma (PXA) is a low-grade astrocytic tumour that occasionally progresses to a higher grade. We have extensively reviewed the literature on the potential for malignant transformation of PXA. An illustrative case of a PXA transforming to glioblastoma multiforme is presented.
Subject(s)
Astrocytoma/pathology , Brain Neoplasms/pathology , Cell Transformation, Neoplastic/pathology , Glioblastoma/pathology , Temporal Lobe/pathology , Adolescent , Adult , Astrocytoma/therapy , Biomarkers, Tumor/metabolism , Brain Neoplasms/therapy , Cell Transformation, Neoplastic/genetics , Child , Combined Modality Therapy/methods , Combined Modality Therapy/standards , Female , Glioblastoma/therapy , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging/standards , Temporal Lobe/surgery , Young AdultABSTRACT
Researchers have longstanding concerns about the logistical and administrative burdens posed by ethics review of multisite studies involving human participants. Centralised ethics review, in which approval by one committee has authority across multiple sites, is widely touted as a strategy for streamlining the process. The Harmonisation of Multi-centre Ethical Review (HoMER) project is currently developing such a system for Australia. It is unclear how centralised review will work for multisite Indigenous health research, where the views of local stakeholders are important and community consultation is mandatory. Our recent experience in conducting the National Indigenous Eye Health Survey (NIEHS) shows how elaborate the current ethics approval and community consultation processes can be, and points to several lessons and ideas to guide pending reforms.
