Predictive biomarkers for drug response in bladder cancer

Yoshida, Takahiro; Kates, Max; Fujita, Kazutoshi; Bivalacqua, Trinity J.; McConkey, David J.

doi:10.1111/iju.14082

Cited by 53 publications

(56 citation statements)

References 79 publications

(205 reference statements)

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“…Molecularly and clinically, BC is a heterogeneous disease. The large scale transcriptomic analysis revealed the existence of the luminal and basal subtypes of MIBC, similarly as it is reported for breast cancer . The basal subtype had much worse prognosis and survival rate than luminal subtype .…”

Section: Introductionsupporting

confidence: 70%

SWI/SNF chromatin remodeling complex and glucose metabolism are deregulated in advanced bladder cancer

et al. 2020

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Bladder cancer (BC) is a frequently diagnosed malignancy affecting predominantly adult and elderly populations. It is expected that due to the longer life time, BC will become even more frequent in the future; thus in consequence, it will represent serious health problem of older society part. The treatment of advanced BC is mostly ineffective due to its very aggressive behavior. So far, no effective targeted therapy is used for BC treatment. Here, we found that BC is characterized by lower protein levels of BRM, INI1, and BAF155 main subunits of SWI/SNF chromatin remodeling complex (CRC) which is involved in global control of gene expression and influences various important cellular processes like: cell cycle control, apoptosis, DNA repair, etc. Moreover, the expression of SMARCA2, a BRM encoding gene, strongly correlated with BC metastasis and expression of such metabolic genes as PKM2 and PRKAA1. Furthermore, the analysis of T24 and 5637 commonly used BC cell lines revealed different expression levels of metabolic genes including FBP1 gene encoding Frutose-1,6-Bisphosphatase, an enzyme controlling glycolysis flux and gluconeogenesis. The tested BC cell lines exhibited various molecular and metabolic alterations as well as differential glucose uptake, growth rate, and migration potential. We have shown that BRM subunit is involved in the transcriptional control of genes encoding metabolic enzymes.Moreover, we found that the FBP1 expression level and the SWI/SNF CRCs may serve as markers of molecular subtypes of BC. Collectively, this study may provide a new knowledge about the molecular and metabolic BC subtypes which likely will be of high importance for the clinic in the future.

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Section: Introductionsupporting

confidence: 70%

SWI/SNF chromatin remodeling complex and glucose metabolism are deregulated in advanced bladder cancer

et al. 2020

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“…Bladder cancer can either be non‐muscle‐invasive (NMIBC) or muscle‐invasive (MIBC). In case of MIBC, radical cystectomy combined with perioperative cisplatin (CDDP)‐based chemotherapy is the standard of care 4,5 . Additionally, the use of neoadjuvant chemotherapy (NAC) has a role in eliminating residual disease in the cystectomy specimen and prolonging patient survival 6 .…”

Section: Introductionmentioning

confidence: 99%

“…Genetic profiling is not only able to identify mutations but also offers targeted therapy 5 . Of interest is the TP53 gene mutation which was found to be responsible for CDDP resistance 5,10 .…”

Section: Introductionmentioning

confidence: 99%

Triple‐marker immunohistochemical assessment of muscle‐invasive bladder cancer: Is there prognostic significance?

et al. 2021

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Background Bladder cancer is the ninth most common cancer worldwide, and the third most common cancer in Lebanon. Immunohistochemistry (IHC) has been used to stratify muscle‐invasive bladder cancer (MIBC) into different subtypes. However, to our knowledge, there exists no study that investigates the use of this low‐cost technique to predict prognosis in bladder cancer patients in our region. Aim To examine the feasibility of low‐cost triple‐marker IHC assessment for MIBC subtyping in order to predict patients' survival and cisplatin sensitivity. Methods and results We collected the specimens of deceased patients diagnosed with MIBC on pathology at our institution. For each case, tumor tissue blocks were retrieved and stained for hematoxylin and eosin in addition to three molecular markers by IHC: cytokeratin 5/6, cytokeratin 14 staining basal BC, and GATA3 staining luminal BC. A cut‐off of ≥20% was set as positive. Kaplan‐Meier curves were built, factored by BC subtype, to predict overall survival (OS), disease‐specific survival (DSS), and progression‐free survival (PFS). Hazard ratios in Cox regression were also created accounting for oncological factors and BC subtype. We categorized specimens as either luminal (GATA3 positive only) (n = 21; 56.7%) or as double‐positive (GATA3 and basal cytokeratin 5/6 or cytokeratin 14 positive) (n = 16; 43.3%). The overall median survival was similar between the two categories (27.0 ± 4.82 months). Numbers favored luminal disease for PFS (Breslow P = .032). After adjusting for covariates, luminal molecular expression predicted PFS (0.28; [0.09‐0.94]). Yet, the Cox model was not able to identify any predictors of OS or DSS. Conclusion Specimens enriched with only a luminal molecular profile were more likely to exhibit cisplatin sensitivity. Despite the absence of guidelines recommending the utilization of molecular profiling in clinic practice, triple‐marker IHC could serve as a potential low‐cost prognostic indicator to identify patients at high risk of progression.

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“…In recent years, immunotherapy had been proven to be an effective strategy for the treatment of advanced and metastatic BC, whether as a monotherapy or in combination with other treatments [28 , 29]. However, even this promising therapy had an overall response rate of only 10% to 30% [30], which indicated the importance of accurately identifying patients who would bene t from these novel drugs [31]. According to reports, patients with advanced BC who had received chemotherapy showed a better response to atezolizumab [15-17 , 20], and the e cacy rate could be increased 34% to 100%.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Responses to Chemotherapy or Immunotherapy by Molecular Subtype in Bladder Cancer Patients: A Meta-Analysis and Systematic Review

Shun-de¹,

Yuan²,

Ge³

et al. 2021

Preprint

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Background Bladder cancer (BC) is a heterogeneous disease characterized by high recurrence and a poor prognosis. Molecular subtypes of BC portend personalized and precision medicine. However, whether there is a difference in therapeutic response to chemotherapy or immunotherapy between different molecular subtypes of BC has not been systematically evaluated.Methods A comprehensive literature search was performed up to October 2020. Consensus clusters 1 (CC1), CC2 and CC3 molecular subtypes were defined according to the heterogeneity and similarity of BC molecular subtypes from published studies to perform meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the therapeutic response, and a fixed- or random-effects model was used according to the existence of heterogeneity.Results Eight studies involving 1463 patients were included in this research. For immunotherapy, CC3 showed the highest respond rate (CC3 vs CC1: OR 0.52, CI [0.34–0.78], P = 0.002. CC3 vs CC2: OR 0.42, CI [0.28–0.62], P < 0.0001), which was mainly reflected in the highest response rate to atezolizumab (CC3 vs CC1: OR 0.47, CI [0.29–0.75], P = 0.002. CC3 vs CC2: OR 0.38, CI [0.24–0.59], P < 0.0001), and the response rates to nivolumab showed no advantage over CC1 and CC2. No difference in response to the two immunotherapies between CC1 and CC2. For chemotherapy, CC3 had the lowest response rate to the overall chemotherapy (CC3 vs CC1: OR 2.28, CI [1.39–3.74], P = 0.001. CC3 vs CC2: OR = 2.25, 95% CI 1.34–3.76, P = 0.002). Compared with CC2, CC3 responded poorly to both neo-adjuvant chemotherapy (NAC) (OR 1.93, CI [1.09–3.41], P = 0.02) and chemoradiation therapy (CRT) (OR 4.53, CI [1.26–16.27], P = 0.02). Compared with CC1, CC3 only showed a poorer response to CRT (OR 6.07, CI [1.87–19.71], P = 0.003), and no difference in NAC. No difference between CC1 and CC2 subtypes in the response rates to NAC and CRT.Conclusions Our study suggested that molecular classifications are important predictors of cancer treatment outcomes of BC patients and could identify subgroup patients who are most likely to benefit from specific cancer treatments.

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Predictive biomarkers for drug response in bladder cancer

Cited by 53 publications

References 79 publications

SWI/SNF chromatin remodeling complex and glucose metabolism are deregulated in advanced bladder cancer

SWI/SNF chromatin remodeling complex and glucose metabolism are deregulated in advanced bladder cancer

Triple‐marker immunohistochemical assessment of muscle‐invasive bladder cancer: Is there prognostic significance?

Therapeutic Responses to Chemotherapy or Immunotherapy by Molecular Subtype in Bladder Cancer Patients: A Meta-Analysis and Systematic Review

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