Emerging antibody-based therapeutic strategies for bladder cancer: A systematic review

Azevedo, Rita; Ferreira, José Alexandre; Peixoto, Andreia; Neves, Manuel; Sousa, Nuno; Lima, Áurea; Santos, Lúcio Lara

doi:10.1016/j.jconrel.2015.07.002

Cited by 28 publications

(21 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Muscle-invasive bladder cancer (MIBC) is amongst the most common and deadliest genitourinary cancer (Witjes et al, 2013). The mainstay treatment includes cisplatin-based regimens (Witjes et al, 2013), which fail to avoid tumour relapse and disease dissemination (Chen et al, 2015;Weight et al, 2009), urging the introduction of predictive biomarkers and novel therapeutics (Azevedo et al, 2015;Ecke, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Taking advantage of their cell surface nature, many cancer-associated glycobiomarkers (CA72-4; CA19-9; CA125 which detects MUC16, CEA) have been exploited for noninvasive cancer detection, follow-up and therapy development (Bottoni and Scatena, 2015;Santos et al, 2014;Silva, 2015). Moreover, alterations in glycosylation often render protein glycoforms holding tremendous potential for targeted therapy (Azevedo et al, 2015;Fernandes et al, 2015;Ferreira et al, 2016b). In this context, it has also been long demonstrated that advanced-stage tumours present significant deregulations in glycosylation pathways, translated by the loss of ABO blood group determinants (Sheinfeld et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeted O‐glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced‐stage bladder tumours

et al. 2017

Self Cite

View full text Add to dashboard Cite

Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation on the cell surface, which may be explored for improving disease management. In a search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for short‐chain O‐glycans commonly found in glycoproteins of human solid tumours. These included the Tn and T antigens and their sialylated counterparts sialyl‐Tn(STn) and sialyl‐T(ST), which are generally associated with poor prognosis. We have also explored the nature of T antigen sialylation, namely the sialyl‐3‐T(S3T) and sialyl‐6‐T(S6T) sialoforms, based on combinations of enzymatic treatments. We observed a predominance of sialoglycans over neutral glycoforms (Tn and T antigens) in bladder tumours. In particular, the STn antigen was associated with high‐grade disease and muscle invasion, in accordance with our previous observations. The S3T and S6T antigens were detected for the first time in bladder tumours, but not in healthy urothelia, highlighting their cancer‐specific nature. These glycans were also overexpressed in advanced lesions, especially in cases showing muscle invasion. Glycoproteomic analyses of advanced bladder tumours based on enzymatic treatments, Vicia villosa lectin‐affinity chromatography enrichment and nanoLC‐ESI‐MS/MS analysis resulted in the identification of several key cancer‐associated glycoproteins (MUC16, CD44, integrins) carrying altered glycosylation. Of particular interest were MUC16 STn+‐glycoforms, characteristic of ovarian cancers, which were found in a subset of advanced‐stage bladder tumours facing the worst prognosis. In summary, significant alterations in the O‐glycome and O‐glycoproteome of bladder tumours hold promise for the development of novel noninvasive diagnostic tools and targeted therapeutics. Furthermore, abnormal MUC16 glycoforms hold potential as surrogate biomarkers of poor prognosis and unique molecular signatures for designing highly specific targeted therapeutics.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeted O‐glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced‐stage bladder tumours

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…More than 90% of bladder cancers are urothelial carcinomas; at diagnosis, approximately 60% of bladder cancers are classified as low-grade non-muscle invasive (NMIBC), whereas the remaining 40% are classified as high-grade muscle-invasive tumors (MIBC; refs. 13,14). Treatment for NMIBC tumors involves transurethral resection, followed by the instillation of chemotherapeutic agents (mitomycin) or an immunostimulatory agent, Bacillus Calmette Guerin, to delay recurrence, and periodical cystoscopic surveillance (15,16).…”

Section: Introductionmentioning

confidence: 99%

Activating Transcription Factor 3 Expression as a Marker of Response to the Histone Deacetylase Inhibitor Pracinostat

Sooraj

Cain

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Improved treatment strategies are required for bladder cancer due to frequent recurrence of low-grade tumors and poor survival rate from high-grade tumors with current therapies. Histone deacetylase inhibitors (HDACi), approved as single agents for specific lymphomas, have shown promising preclinical results in solid tumors but could benefit from identification of biomarkers for response. Loss of activating transcription factor 3 (ATF3) expression is a feature of bladder tumor progression and correlates with poor survival. We investigated the utility of measuring ATF3 expression as a marker of response to the HDACi pracinostat in bladder cancer models. Pracinostat treatment of bladder cancer cell lines reactivated the expression of ATF3, correlating with significant alteration in proliferative, migratory, and anchoragedependent growth capacities. Pracinostat also induced growth arrest at the G 0 -G 1 cell-cycle phase, coincident with the activation of tumor suppressor genes. In mouse xenograft bladder cancer models, pracinostat treatment significantly reduced tumor volumes compared with controls, accompanied by reexpression of ATF3 in nonproliferating cells from early to late stage of therapy and in parallel induced antiangiogenesis and apoptosis. Importantly, cells in which ATF3 expression was depleted were less sensitive to pracinostat treatment in vitro, exhibiting significantly higher proliferative and migratory properties. In vivo, control xenograft tumors were significantly more responsive to treatment than ATF3 knockdown xenografts. Thus, reactivation of ATF3 is an important factor in determining sensitivity to pracinostat treatment, both in vitro and in vivo, and could serve as a potential biomarker of response and provide a rationale for therapeutic utility in HDACi-mediated treatments for bladder cancer.

show abstract

“…These nanodelivery sytems may include conventional chemotherapy drugs, genetic-based strategies such as the siRNAs against key oncogenic proteins involved in chemoresistance (Ganesh S et al, 2013;Navarro G et al, 2012;QingShuo M et al, 2013) or the administration of genes capable of rescuing the expression of p53 and other cell cycle checkpoint proteins (Chen GX et al, 2014;Kamal A et al, 2014;Kim SS et al, 2014;Li D et al, 2013). The introduction of antibodies against cancer-associated glycoepitopes may also allow the selective inhibition of oncogenic pathways or the stimulation of immune responses against malignant cells (Azevedo R et al, 2015). Glycan-based therapeutic solutions should also be tested, for the first time, in the context of hematological malignancies that also pose significant chemoresistance issues (Assaraf YG et al, 2014;Assaraf YG, 2007;Gonen N and Assaraf YG, 2012).…”

Section: Future Perspectivesmentioning

confidence: 99%

Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation

Ferreira

Peixoto

Neves

et al. 2016

Drug Resistance Updates

Self Cite

130

View full text Add to dashboard Cite

Cisplatin-based chemotherapeutic regimens are the most frequently used (neo)adjuvant treatments for the majority of solid tumors. While platinum-based chemotherapeutic regimens have proven effective against highly proliferative malignant tumors, significant relapse and progression rates as well as decreased overall survival are still observed. Currently, it is known that sub-populations of chemoresistant cells share biological properties with cancer stem cells (CSC), which are believed to be responsible for tumor relapse, invasion and ultimately disease dissemination through acquisition of mesenchymal cell traits. In spite of concentrated efforts devoted to decipher the mechanisms underlying CSC chemoresistance and to design targeted therapeutics to these cells, proteomics has failed to unveil molecular signatures capable of distinguishing between malignant and non-malignant stem cells. This has hampered substantial developments in this complex field. Envisaging a novel rationale for an effective therapy, the current review summarizes the main cellular and molecular mechanisms underlying cisplatin resistance and the impact of chemotherapy challenge in CSC selection and clinical outcome. It further emphasizes the growing amount of data supporting a role for protein glycosylation in drug resistance. The dynamic and context-dependent nature of protein glycosylation is also comprehensively discussed, hence highlighting its potentially important role as a biomarker of CSC. As the paradigm of cancer therapeutics shifts towards precision medicine and patient-tailored therapeutics, we bring into focus the need to introduce glycomics and glycoproteomics in holistic pan-omics models, in order to integrate diverse, multimodal and clinically relevant information towards more effective cancer therapeutics.

show abstract

Emerging antibody-based therapeutic strategies for bladder cancer: A systematic review

Cited by 28 publications

References 154 publications

Targeted O‐glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced‐stage bladder tumours

Targeted O‐glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced‐stage bladder tumours

Activating Transcription Factor 3 Expression as a Marker of Response to the Histone Deacetylase Inhibitor Pracinostat

Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation

Contact Info

Product

Resources

About