RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway

Yan, Xinmin; Chen, Jie; Meng, You; He, Chao; Zou, Shitao; Li, Peng; Chen, Ming; Wu, Jinchang; Ding, Wei‐Qun; Zhou, Jundong

doi:10.1002/cam4.2203

Cited by 17 publications

(23 citation statements)

References 35 publications

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“…The correlation between protein levels of specific genes and response to nCRT in rectal cancer has been extensively investigated by immunohistochemistry analysis of single candidate proteins and by explorative, proteomic approaches. The identified protein biomarkers are involved in diverse biological processes, such as DNA repair, 87 oncogenic signaling, 88 or apoptosis. 89 A selection of predictive, tissue-based protein markers is summarized in Table 2 .…”

Section: Introductionmentioning

confidence: 99%

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

Xiao

Venkatachalam

et al. 2022

Ther Adv Med Oncol

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Colorectal cancer (CRC) is a major contributor to cancer-associated morbidity worldwide and over one-third of CRC is located in the rectum. Neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection is commonly applied to treat locally advanced rectal cancer (LARC). In this review, we summarize current and novel concepts of neoadjuvant therapy for LARC such as total neoadjuvant therapy and describe how these developments impact treatment response. Moreover, as response to nCRT is highly divergent in rectal cancers, we discuss the role of potential predictive biomarkers. We review recent advances in biomarker discovery, from a clinical as well as a histopathological and molecular perspective. Furthermore, the role of emerging predictive biomarkers derived from the tumor environment such as immune cell composition and gut microbiome is presented. Finally, we describe how different tumor models such as patient-derived cancer organoids are used to identify novel predictive biomarkers for chemoradiotherapy (CRT) in rectal cancer.

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Section: Introductionmentioning

confidence: 99%

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

Xiao

Venkatachalam

et al. 2022

Ther Adv Med Oncol

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“…RAD18 promotes the migration and invasion of esophageal squamous cell cancer via the JNK-MMPs pathway [ 9 ]. RAD18 high predicts the poor response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer [ 10 ]. Nevertheless, the role of RAD18 in breast cancer has not been well explored.…”

Section: Introductionmentioning

confidence: 99%

A positive feedback loop: RAD18-YAP-TGF-β between triple-negative breast cancer and macrophages regulates cancer stemness and progression

Yan

Yang

et al. 2022

Cell Death Discov.

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As a key regulator of the DNA translesion synthesis (TLS) pathway, RAD18 is error-prone and contributes to the accumulation of DNA mutations. Our previous study showed that it plays an essential role in the progression of multiple tumors. However, the mechanism through which RAD18 influences triple-negative breast cancer (TNBC), especially the interaction between tumor cells and the tumor microenvironment, remains elusive. In this study, we showed that RAD18 expression is markedly higher in patients with high T stage TNBC and inversely correlated with prognosis. High expression of RAD18 facilitated a highly stem-cell phenotype through the Hippo/YAP pathway, which supports the proliferation of TNBC. In addition, the cytokine byproduct TGF-β activates macrophages to have an M2-like tumor-associated macrophage (TAM) phenotype. Reciprocally, TGF-β from TAMs activated RAD18 in TNBC to enhance tumor stemness, forming a positive feedback loop. Inhibition of YAP or TGF-β breaks this loop and suppresses cancer stemness and proliferation In nude mice, RAD18 promoted subcutaneous transplanted tumor growth and M2-type TAM recruitment. Collectively, the RAD18-YAP-TGF-β loop is essential for the promotion of the stemness phenotype by TNBC and could be a potential therapeutic target for TNBC.

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“…RAD18, an E3 ubiquitin-linked enzyme, has a role in maintaining genome stability through multiple DNA repair pathways, including HR and PPR [22][23][24]. Several studies have shown that high expression of RAD18 confers resistance to chemotherapy or radiotherapy in multiple human cancers [25][26][27]. Thus, targeted inhibition of DNA repair proteins could affect drug response and improve therapy efficacy [28,29].…”

Section: Dysregulation Of Dna Repair Genes and Drug Responsementioning

confidence: 99%

Yeast-based assays for the functional characterization of cancer-associated variants of human DNA repair genes

et al. 2020

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Technological advances are continuously revealing new genetic variants that are often difficult to interpret. As one of the most genetically tractable model organisms, yeast can have a central role in determining the consequences of human genetic variation. DNA repair gene mutations are associated with many types of cancers, therefore the evaluation of the functional impact of these mutations is crucial for risk assessment and for determining therapeutic strategies. Owing to the evolutionary conservation of DNA repair pathways between human cells and the yeast Saccharomyces cerevisiae, several functional assays have been developed. Here, we describe assays for variants of human genes belonging to the major DNA repair pathways divided in functional assays for human genes with yeast orthologues and human genes lacking a yeast orthologue. Human genes with orthologues can be studied by introducing the correspondent human mutations directly in the yeast gene or expressing the human gene carrying the mutations; while the only possible approach for human genes without a yeast orthologue is the heterologous expression. The common principle of these approaches is that the mutated gene determines a phenotypic alteration that can vary according to the gene studied and the domain of the protein. Here, we show how the versatility of yeast can help in classifying cancer-associated variants.

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RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway

Cited by 17 publications

References 35 publications

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

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

A positive feedback loop: RAD18-YAP-TGF-β between triple-negative breast cancer and macrophages regulates cancer stemness and progression

Yeast-based assays for the functional characterization of cancer-associated variants of human DNA repair genes

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