Tumor heterogeneity and the potential role of liquid biopsy in bladder cancer

Huang, Haiming; Li, Hai-Xia

doi:10.1002/cac2.12129

Cited by 39 publications

(29 citation statements)

References 115 publications

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“…The management of MIBC or very-high-risk NMIBC involves radical cystectomy and cisplatin-based chemotherapy [ 4 ]. Unfortunately, treatment failure is observed in more than 50% of the patients due to the associated comorbidities and inherent or acquired chemoresistance [ 5 , 6 ]; leading to poor prognosis, with a median progression-free survival (PFS) and overall survival (OS) of ∼8 and 14 months, respectively [ 7 ]. Therefore, a better understanding of the mechanisms involved in UCB tumorigenesis and/or progression is required for developing more efficient treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis

et al. 2021

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Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.

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Section: Introductionmentioning

confidence: 99%

LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis

et al. 2021

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“…One that is directly relevant to this manuscript pertains to its potential to capture intra- and intertumoral genetic heterogeneity. Because ctDNA reflects the released DNA from tumor cells throughout a given tumor mass (intratumoral heterogeneity) and across multiple tumor masses (spatial intertumoral heterogeneity) in a patient, its analysis in theory will reflect the total genetic composition of all tumor masses, which is in contrast to analysis of tissue [ 36 , 37 ]. While in our manuscript, we analyzed up to six tumor masses from a single patient, this is not feasible on a routine clinical basis.…”

Section: Discussionmentioning

confidence: 99%

Recommendations for Specimen and Therapy Selection in Colorectal Cancer

et al. 2021

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Introduction Next-generation sequencing has emerged as a clinical tool for the identification of actionable mutations to triage advanced colorectal cancer patients for targeted therapies. The literature is conflicted as to whether primaries or their metastases should be selected for sequencing. Some authors suggest that either site may be sequenced, whereas others recommend sequencing the primary, the metastasis, or even both tumors. Here, we address this issue head on with a meta-analysis and provide for the first time a set of sensible recommendations to make this determination. Methods From our own series, we include 43 tumors from 13 patients including 14 primaries, 10 regional lymph node metastases, 17 distant metastases, and two anastomotic recurrences sequenced using the 50 gene Ion AmpliSeq cancer NGS panel v2. Results Based on our new cohort and a meta-analysis, we found that ~ 77% of patient-matched primary-metastatic pairs have identical alterations in these 50 cancer-associated genes. Conclusions Low tumor cellularity, tumor heterogeneity, clonal evolution, treatment status, sample quality, and/or size of the sequencing panel accounted for a proportion of the differential detection of mutations at primary and metastatic sites. The therapeutic implications of the most frequently discordant alterations ( TP53 , APC , PIK3CA , and SMAD4 ) are discussed. Our meta-analysis indicates that a subset of patients who fail initial therapy may benefit from sequencing of additional sites to identify new actionable genomic abnormalities not present in the initial analysis. Evidence-based recommendations are proposed. Supplementary Information The online version contains supplementary material available at 10.1007/s40487-021-00151-7.

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“…Encountered regularly in clinical practice, bladder cancer has a high risk of recurrence and a high mutation rate. Owing to the heterogeneity of this tumor, the prognosis is poor [ 114 ]. Culture systems for bladder cancer organoids have been mentioned in many studies [ 115 , 116 ].…”

Section: Applications Of Organoids In Various Types Of Cancermentioning

confidence: 99%

Tumor organoids: synergistic applications, current challenges, and future prospects in cancer therapy

Kalyani

Liu

et al. 2021

Cancer Communications

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Patient-derived cancer cells (PDCs) and patient-derived xenografts (PDXs) are often used as tumor models, but have many shortcomings. PDCs not only lack diversity in terms of cell type, spatial organization, and microenvironment but also have adverse effects in stem cell cultures, whereas PDX are expensive with a low transplantation success rate and require a long culture time. In recent years, advances in three-dimensional (3D) organoid culture technology have led to the development of novel physiological systems that model the tissues of origin more precisely than traditional culture methods. Patient-derived cancer organoids bridge the conventional gaps in PDC and PDX models and closely reflect the pathophysiological features of natural tumorigenesis and metastasis, and have led to new patient-specific drug screening techniques, development of individualized treatment regimens, and discovery of prognostic biomarkers and mechanisms of resistance. Synergistic combinations of cancer organoids with other technologies, for example, organ-on-a-chip, 3D bio-printing, and CRISPR-Cas9-mediated homology-independent organoid transgenesis, and with

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Tumor heterogeneity and the potential role of liquid biopsy in bladder cancer

Cited by 39 publications

References 115 publications

LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis

LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis

Recommendations for Specimen and Therapy Selection in Colorectal Cancer

Tumor organoids: synergistic applications, current challenges, and future prospects in cancer therapy

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