Predicting response to neoadjuvant chemoradiotherapy in rectal cancer: from biomarkers to tumor models

Li, Moying; Xiao, Qiuping; Venkatachalam, Nachiyappan; Hofheinz, Ralf–Dieter; Veldwijk, Marlon R.; Herskind, Carsten; Ebert, Matthias; Zhan, Tianzuo

doi:10.1177/17588359221077972

Cited by 38 publications

(29 citation statements)

References 211 publications

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“…In cases of CRC, multidrug chemotherapy (e.g., fluorouracil plus oxaliplatin, fluorouracil plus irinotecan, and fluorouracil plus oxaliplatin/capecitabine and oxaliplatin) is widely used as standard treatment; however, its efficacy varies from patient to patient [ 1 ]. While preoperative neoadjuvant CRT is used to treat locally advanced rectal cancer, treatment response remains highly variable [ 92 ]. Using PDOs to classify CRC patients with diverse biological characteristics thus appears to be an effective method to achieve better responses to chemotherapy and radiotherapy.…”

Section: Patient-derived Organoids As Predictive Biomarkers In Cancer...mentioning

confidence: 99%

Patient-Derived Organoids of Colorectal Cancer: A Useful Tool for Personalized Medicine

Kiwaki

Kataoka

2022

JPM

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Colorectal cancer is one of the most important malignancies worldwide, with high incidence and mortality rates. Several studies have been conducted using two-dimensional cultured cell lines; however, these cells do not represent a study model of patient tumors very well. In recent years, advancements in three-dimensional culture methods have facilitated the establishment of patient-derived organoids, which have become indispensable for molecular biology-related studies of colorectal cancer. Patient-derived organoids are useful in both basic science and clinical practice; they can help predict the sensitivity of patients with cancer to chemotherapy and radiotherapy and provide the right treatment to the right patient. Regarding precision medicine, combining gene panel testing and organoid-based screening can increase the effectiveness of medical care. In this study, we review the development of three-dimensional culture methods and present the most recent information on the clinical application of patient-derived organoids. Moreover, we discuss the problems and future prospects of organoid-based personalized medicine.

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Section: Patient-derived Organoids As Predictive Biomarkers In Cancer...mentioning

confidence: 99%

Patient-Derived Organoids of Colorectal Cancer: A Useful Tool for Personalized Medicine

Kiwaki

Kataoka

2022

JPM

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“…Recently, specific research or protocols on the organoid model of RC is gradually garnering attention from scientists in the last two years, and translational applications are springing up ( 16 , 39 – 41 )( Table 2 ). The translational application of the RC PDO model is also mentioned in some recent literature and systematic reviews ( 44 , 46 , 50 , 52 , 53 ). There is a need for standard procedures and methods to improve the reproducibility and stability during laboratory practice.…”

Section: Introductionmentioning

confidence: 99%

Patient-derived rectal cancer organoids—applications in basic and translational cancer research

Yan

Cheong²,

Chen³

et al. 2022

Front. Oncol.

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Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and among the leading causes of death in both men and women. Rectal cancer (RC) is particularly challenging compared with colon cancer as the treatment after diagnosis of RC is more complex on account of its narrow anatomical location in the pelvis adjacent to the urogenital organs. More and more existing studies have begun to refine the research on RC and colon cancer separately. Early diagnosis and multiple treatment strategies optimize outcomes for individual patients. However, the need for more accurate and precise models to facilitate RC research is underscored due to the heterogeneity of clinical response and morbidity interrelated with radical surgery. Organoids generated from biopsies of patients have developed as powerful models to recapitulate many aspects of their primary tissue, consisting of 3-D self-organizing structures, which shed great light on the applications in both biomedical and clinical research. As the preclinical research models for RC are usually confused with colon cancer, research on patient-derived RC organoid models enable personalized analysis of cancer pathobiology, organizational function, and tumor initiation and progression. In this review, we discuss the various applications of patient-derived RC organoids over the past two years in basic cancer biology and clinical translation, including sequencing analysis, drug screening, precision therapy practice, tumor microenvironment studies, and genetic engineering opportunities.

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“…Many studies have been devoted to identify predictive factors present in tumors before treatment. However, gene expression studies have failed to provide reproducible and clinically useful information for the identification of patients who could benefit from nCRT [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Predictive value of proteomic markers for advanced rectal cancer with neoadjuvant chemoradiotherapy

Wang

Tian

et al. 2022

BMC Cancer

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Background Preoperative neoadjuvant chemoradiation (nCRT) has been the standard treatment for locally advanced rectal cancer. Serum biomarkers to stratify patients with respect to prognosis and response to nCRT are needed due to the diverse response to the therapy. Methods Thirteen paired pre- and post-nCRT sera from rectal cancer patients were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) method. Twenty-five proteins were selected for validation by parallel reaction monitoring (PRM) in ninety-one patients. Results Totally, 310 proteins were identified and quantified in sera samples. Reactome pathway analysis showed that the immune activation-related pathways were enriched in response to nCRT. Twenty-five proteins were selected for further validation. PRM result showed that the level of PZP was higher in pathological complete response (pCR) patients than non-pCR patients. The Random Forest algorithm identified a prediction model composed of 10 protein markers, which allowed discrimination between pCR patients and non-pCR patients (area under the curve (AUC) = 0.886 on testing set). Higher HEP2 and GELS or lower S10A8 in baseline sera were associated with better prognosis. Higher APOA1 in post nCRT sera was associated with better disease-free survival (DFS). Conclusions We identified and confirmed a 10-protein panel for nCRT response prediction and four potential biomarkers HEP2, GELS, S10A8 and APOA1 for prognosis of rectal cancer based on iTRAQ-based comparative proteomics screening and PRM-based targeted proteomic validation.

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Predicting response to neoadjuvant chemoradiotherapy in rectal cancer: from biomarkers to tumor models

Cited by 38 publications

References 211 publications

Patient-Derived Organoids of Colorectal Cancer: A Useful Tool for Personalized Medicine

Patient-Derived Organoids of Colorectal Cancer: A Useful Tool for Personalized Medicine

Patient-derived rectal cancer organoids—applications in basic and translational cancer research

Predictive value of proteomic markers for advanced rectal cancer with neoadjuvant chemoradiotherapy

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