Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success. To improve clinical outcomes, translational models predictive of drug response are needed. We describe a simple method for the fast establishment of CRC patient-derived explant (CRC-PDE) cultures from different carcinogenesis pathways, employing agitation-based platforms. A total of 26 CRC-PDE were established and a subset was evaluated for viability (n = 23), morphology and genetic key alterations (n = 21). CRC-PDE retained partial tumor glandular architecture and microenvironment features were partially lost over 4 weeks of culture. Key proteins (p53 and Mismatch repair) and oncogenic driver mutations of the original tumours were sustained throughout the culture. Drug challenge (n = 5) revealed differential drug response from distinct CRC-PDE cases. These findings suggest an adequate representation of the original tumour and highlight the importance of detailed model characterisation. The preservation of key aspects of the CRC microenvironment and genetics supports CRC-PDE potential applicability in pre- and co-clinical settings, as long as temporal dynamics are considered.

Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management

“…PDEs have been widely used for the evaluation of tumor response to chemotherapeutics, modeling clinical treatments that patients may receive as SOC ( 30 , 56 , 60 ). The possibility of resistance to chemotherapies means it is useful to test multiple regimens, where they are available, to determine the treatment(s) most likely to be effective for the individual patient.…”

Phytochemical Profiles and Anticancer Effects of Calophyllum inophyllum L. Extract Relating to Reactive Oxygen Species Modulation on Patient-Derived Cells from Breast and Lung Cancers

“…The PDCs offer distinct advantages over immortalized cell lines, as they faithfully preserve the cellular assembly, tissue architecture, microenvironment, and cancer niches found in the body. This unique characteristic enables PDCs to exhibit more accurate responses to cytotoxic compounds and enhanced detection of cancer markers, surpassing traditional cell lines [ 35 ]. A notable biomarker associated with cancer cell proliferation and metastasis is Ki-67, which is highly expressed in malignant breast and lung cancer cells but is minimally detected in normal proliferating cells [ 36 ].…”

Patient-Derived Xenograft: A More Standard “Avatar” Model in Preclinical Studies of Gastric Cancer

“…Gastric cancer PDX models transplanted in mice run the risk that human-derived stromal components may be progressively assimilated by the mouse due to the altered growth environment, with gradual differences between the transplanted and primary tumor tissues ( 33 , 34 ). This discrepancy will affect the reliability of research results, so how to avoid or reduce this loss of human-derived stroma is of particular importance.…”