scholarly journals Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

2019 ◽  
Vol 20 (4) ◽  
pp. 793 ◽  
Author(s):  
Jennifer Tse ◽  
Rashed Ghandour ◽  
Nirmish Singla ◽  
Yair Lotan
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Tyrosine Kinases ◽  
Standard Of Care ◽  
Complete Response ◽  
Pathological Examination ◽  
Current State ◽  
Response To Chemotherapy ◽  
Carcinoma Of The Bladder ◽  
Repair Genes

Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation. Molecular markers have been evaluated to try to predict response to chemotherapy to reduce unnecessary treatment and expedite different treatment for nonresponders. A variety of potential biomarkers have been evaluated to predict response to cisplatin based chemotherapy including DNA repair genes (ATM, RB1, FANCC, ERCC2, BRCA1, and ERCC1), regulators of apoptosis (survivin, Bcl-xL, and emmprin), receptor tyrosine kinases (EGFR and erbB2), genes involved in cellular efflux (MDR1 and CTR1), in addition to molecular subtypes (Basal, luminal, and p53-like). The current state of the literature on the prediction of response to NAC based on the presence of these biomarkers is discussed in this review.

The Use of Neoadjuvant Chemotherapy in Patients With Urothelial Carcinoma of the Bladder: Current Practice Among Clinicians

2017 ◽  
Vol 15 (3) ◽  
pp. 356-362 ◽  
Author(s):  
Thomas Martini ◽  
Christian Gilfrich ◽  
Roman Mayr ◽  
Maximilian Burger ◽  
Armin Pycha ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Current Practice ◽  
Carcinoma Of The Bladder

Combination of individual tumor gene expression profiles and quantitative ultrasound and mammography imaging to understand the response to neoadjuvant chemotherapy among Hispanic-Latina women with early stages of triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12605-e12605
Author(s):  
Alexander Philipovskiy ◽  
Sumit Gaur ◽  
Karen Chambers ◽  
Roberto Gamez ◽  
Renato Aguilera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Tumor Response ◽  
Residual Disease ◽  
Complete Response ◽  
Response To Chemotherapy ◽  
Before And After ◽  
The Individual

e12605 Background: Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) characterized by the absence of targetable receptors. Traditionally, neoadjuvant chemotherapy (NACT) has been used to downstage the tumors and increase the chance for breast-conserving surgery. The pathological complete response (pCR) has been traditionally considering the best predictive marker for the disease recurrence. Patients with residual disease (RD) have a poor prognosis with a high risk of recurrence, and therefore additional chemotherapy was recommended. Therefore it is an important task for clinical researchers to identify markers to predict the individual tumor response to chemotherapy and avoid in patients potentially resistant tumors. Instead, a surgical approach can be used or combined approach with chemotherapy and immunotherapy. It is not clear yet which approach is optimal for those patients with chemotherapy-resistant tumors since there is no clinical data available and no clinical tool that helps predict the individual tumor response. In this study, we examined breast ultrasound(US) images of patients before and after the completion of NACT and correlated with response to chemotherapy. To better understand the biology of resistance to chemotherapy, we also analyzed the gene expression profile of 15 patients with RD after NACT. Methods: In this study, we retrospective analyzed breast US data from 37 Hispanic patients diagnosed with TNBC and treated with NACT. Patients underwent breast US before and after NACT with documentation of clinical complete response (cCR) or clinical residual disease (cRD). Post-operatively, the pathologic response was defined as the absence of tumor cells (pCR) or presence of residual invasive tumor (RD). A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR. Also, we analyzed formalin-fixed paraffin-embedded tumor samples from 15 patients with RD after NACT. Results: Seventeen patients (45.9%) achieved pCR, and twenty (54.1%) had RD after NACT. The most common US findings connected with RD was the deposition of calcium before NACT six (30%) patients. Gene expression analysis of RD samples identified 446 upregulated and 275 downregulated genes. Among commonly upregulated genes related to cancer, we identified GLI1, IGF1, SERPINE1, ATF3, KLK 5; 7, and TUBB2b, and genes belonging to pathways encoding extracellular matrix–related proteins, DNA-damage response proteins, and pathways related to resistance to chemotherapeutic agents such as Taxol. Conclusions: Our data suggested that gene expression profiling in combination with imaging study can be used to identify patients with TNBC potentially resistant to chemotherapy.

scholarly journals Aristolochic Acid and Immunotherapy for Urothelial Carcinoma: Directions for unmet Needs

2019 ◽  
Vol 20 (13) ◽  
pp. 3162 ◽  
Author(s):  
Huang-Yu Yang ◽  
Chih-Chao Yang ◽  
Chao-Yi Wu ◽  
Li-Jen Wang ◽  
Kun-Lin Lu
Keyword(s):  
Urothelial Carcinoma ◽  
Somatic Mutations ◽  
Aristolochic Acid ◽  
Suppressor Gene ◽  
Immune Checkpoint Blockade ◽  
Current State ◽  
Close Relationship ◽  
Tp53 Tumor Suppressor Gene ◽  
Treatment Responses ◽  
Carcinoma Of The Bladder

Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) used to share management with similar principles. However, their genetic and epigenetic differences along with different responses to immunotherapy were recently identified, which are reminiscent of their distinct etiologies. Different from the variety of environmental factors relating to UCB, UTUC is best known for its close relationship with exposure to aristolochic acid (AA). AA is believed to cause its carcinogenicity through forming DNA adducts of deoxyadenosine-aristolactam, as well as A:T → T:A transversions in the TP53 tumor suppressor gene. Since recent findings suggested that cancers with higher somatic mutations are associated with better treatment responses upon immune checkpoint blockade, UTUC and AA-related biomarkers reasonably serve as good candidates, as well as a potential prognostic predictor for the flourishing immunotherapy. This review covers the current state of the literature on the clinical response of UTUC and UCB receiving immunotherapy and points out directions for refinement regarding patient selection.

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