Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas

Burden, Roberta E.; Gormley, Julie A.; Kuehn, Diana; Ward, Claire; Kwok, Hang Fai; Gazdoiu, Mihaela; McClurg, Angela; Jaquin, Thomas J.; Johnston, James A.; Scott, Christopher J.; Olwill, Shane A.

doi:10.1016/j.biochi.2011.08.017

Cited by 45 publications

(38 citation statements)

References 36 publications

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“…A more comprehensive approach could be to decipher dysregulation that brings about distress in the form of diseases. This knowledge can then be used for therapeutic approaches in which excessive and pathogenic protease activities are blocked or, in turn, when proteases become excessively activated or aberrantly cleave substrates (Blum 2008;Burden et al 2012;Coussens et al 2002;Deu et al 2012;Gansz et al 2013;Groth-Pedersen and Jaattela 2013;Guay et al 2010;Hook et al 2010;Lah et al 2006;Mason and Joyce 2011;Palermo and Joyce 2008;Puri and Bogyo 2013;Quail and Joyce 2013;Shen 2012;Sloane et al 2013;Turk 2006). It is therefore evident that our future endeavors to understand the roles of proteases in health and disease must be of an inter-disciplinary nature, merging biochemical and cell biological approaches together in order to understand protease function in a global cellular context.…”

Section: The Protease Family Businessmentioning

confidence: 98%

Proteolysis mediated by cysteine cathepsins and legumain—recent advances and cell biological challenges

et al. 2014

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Proteases play essential roles in protein degradation, protein processing, and extracellular matrix remodeling in all cell types and tissues. They are also involved in protein turnover for maintenance of homeostasis and protein activation or inactivation for cell signaling. Proteases range in function and specificity, with some performing distinct substrate cleavages, while others accomplish proteolysis of a wide range of substrates. As such, different cell types use specialized molecular mechanisms to regulate the localization of proteases and their function within the compartments to which they are destined. Here, we focus on the cysteine family of cathepsin proteases and legumain, which act predominately within the endo-lysosomal pathway. In particular, recent knowledge on cysteine cathepsins and their primary regulator legumain is scrutinized in terms of their trafficking to endo-lysosomal compartments and other less recognized cellular locations. We further explore the mechanisms that regulate these processes and point to pathological cases which arise from detours taken by these proteases. Moreover, the emerging biological roles of specific forms and variants of cysteine cathepsins and legumain are discussed. These may be decisive, pathogenic, or even deadly when localizing to unusual cellular compartments in their enzymatically active form, because they may exert unexpected effects by alternative substrate cleavage. Hence, we propose future perspectives for addressing the actions of cysteine cathepsins and legumain as well as their specific forms and variants. The increasing knowledge in non-canonical aspects of cysteine cathepsin- and legumain-mediated proteolysis may prove valuable for developing new strategies to utilize these versatile proteases in therapeutic approaches.

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Section: The Protease Family Businessmentioning

confidence: 98%

Proteolysis mediated by cysteine cathepsins and legumain—recent advances and cell biological challenges

et al. 2014

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“…Inhibition of cathepsin S using a selective monoclonal antibody Fsn0503 showed a reduction in cell invasion in colorectal, prostate, and breast cell lines, as well as demonstrating attenuation of angiogenesis. Fsn0503 inhibition of cathepsin S in vivo has shown a significant decrease in tumour growth in colorectal tumour models as a single agent (Burden et al, 2009;Vázquez et al, 2014), or in combination with chemotherapy (Burden et al, 2012).…”

Section: Cancermentioning

confidence: 99%

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Wilkinson

Williams

Scott

et al. 2015

Biological Chemistry

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161

137

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Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.

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“…In order to answer this question, researchers further investigated whether Cathepsin S expression levels were affected by chemotherapy in human cancer cell lines using RT-PCR and colorectal xenograft models to analyze the effects of the combination therapy (Cathepsin S inhibitory antibody + CPT11) on tumor progression and on tumor vascularization by immunohistochemical staining of tumors. The results showed that chemotherapy can actually increase the expression of Cathepsin S and that when administered as a combination regimen, the Cathepsin S inhibitory antibody sig-nificantly enhanced the efficacy of CPT-11 [14]. Collectively, these observations clearly show that Cathepsin S inhibitory antibody has the potential to be combined with existing therapeutic strategies for the treatment of cancer.…”

Section: Inhibition Of Cathepsin S By Its Inhibitory Antibody Enchancmentioning

confidence: 83%

Antibody research targeting Cathepsin S for cancer therapy

Kwok¹

2013

ABB

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Cathepsin S is a cysteine protease highly expressed in many type of cancers including colorectal, prostate, breast, and glioblastoma's. It is involved in tumor progression through extracellular matrix remodeling. In recent years, antibody research specifically targeting Cathepsin S to block/inhibit tumorigenic effects were generated some positive preclinical data. This antagonistic antibody was demonstrating efficacy in multiple in vitro/in vivo cancer models both as a monotherapy and in combination with approved agents. This mini-review provides an overview of therapeutic antibody targeting Cathepsin S strategies in the last half decade, focusing on the rationale of cell-surface Cathepsin S targeted and their potential clinical application.

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Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas

Cited by 45 publications

References 36 publications

Proteolysis mediated by cysteine cathepsins and legumain—recent advances and cell biological challenges

Proteolysis mediated by cysteine cathepsins and legumain—recent advances and cell biological challenges

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Antibody research targeting Cathepsin S for cancer therapy

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