Cathepsin B as a target in cancer therapy and imaging

Li, Xin; Shen, Yikai

doi:10.1039/d2nj03037c

Cited by 5 publications

(7 citation statements)

References 106 publications

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“…However, recent advances in imaging tools that target cathepsin B have been proposed, which can help distinguish tumour boundaries and guide surgical early diagnosis of tumours [ 46 ]. In addition, pro-drugs and other target therapeutic agents that respond to cathepsin B have been proposed and used in cancer treatment, and some of them are already on the market [ 46 , 47 ]. Therefore, further research is needed to develop more selective and potent inhibitors for cathepsin B and to investigate the clinical utility or benefit of any cathepsin B inhibitors [ 41 ].…”

Section: Reviewmentioning

confidence: 99%

“…Moreover, targeting cathepsin B alone may not be sufficient to eliminate tumours, and a multifaceted approach targeting multiple molecules or using a combination of chemotherapy or radiation along with targeting cathepsin B may be more appropriate [12]. However, recent advances in imaging tools that target cathepsin B have been proposed, which can help distinguish tumour boundaries and guide surgical early diagnosis of tumours [46]. In addition, pro-drugs and other target therapeutic agents that respond to cathepsin B have been proposed and used in cancer treatment, and some of them are already on the market [46,47].…”

Section: Challenges and Future Directions In Cathepsin B-targeted The...mentioning

confidence: 99%

Section: Challenges and Future Directions In Cathepsin B-targeted The...mentioning

confidence: 99%

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Role of Cathepsin B Expression in Oral Squamous Cell Carcinoma: A Comprehensive Review

Sagar,

Gadkari,

Hiwale

et al. 2024

Cureus

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This comprehensive review delves into the intricate landscape of oral squamous cell carcinoma (OSCC) by examining the role of cathepsin B expression in its pathogenesis. OSCC, a prevalent and clinically significant oral malignancy, poses a considerable global health burden, necessitating a thorough exploration of its underlying molecular mechanisms. Cathepsin B, a lysosomal cysteine protease, emerges as a critical player in OSCC, influencing tumour initiation, invasion, and metastasis. The review begins with a brief overview of OSCC, emphasizing its epidemiological and clinical features, followed by exploring the significance of studying cathepsin B expression in this context. In the manuscript, the structure and function of cathepsin B are elucidated, providing a foundation for understanding its aberrant expression in OSCC. Clinical studies revealing correlations with tumour grade and stage, along with prognostic significance, are scrutinized, offering insights into the potential diagnostic and prognostic utility of cathepsin B. The biological functions of cathepsin B in OSCC, including its impact on tumour invasion and modulation of apoptosis, are comprehensively discussed. The Therapeutic Implications section explores targeting cathepsin B as a potential strategy, emphasizing the need for future research to overcome associated challenges. In the Conclusion section, the review synthesizes key findings, delineates implications for future research, and highlights the potential impact of cathepsin B on OSCC diagnosis and treatment, contributing to the ongoing efforts to advance our understanding of this complex malignancy, which is associated with a high mortality rate and improve clinical outcomes.

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Section: Reviewmentioning

confidence: 99%

Section: Challenges and Future Directions In Cathepsin B-targeted The...mentioning

confidence: 99%

Section: Challenges and Future Directions In Cathepsin B-targeted The...mentioning

confidence: 99%

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Role of Cathepsin B Expression in Oral Squamous Cell Carcinoma: A Comprehensive Review

Sagar,

Gadkari,

Hiwale

et al. 2024

Cureus

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“…Investigations into the cathepsin B enzyme in tumor tissue have attracted a lot of attention, since it plays a pivotal role in tumor invasion and metastasis. Much recent pharmacological research has been focused on targeting overexpressed cathepsin B in cancer cells [9,10]. Researchers have mainly utilized the peptide-cleavage ability of cathepsin B enzymes [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Development of a Peptide-Based Nano-Sized Cathepsin B Inhibitor for Anticancer Therapy

et al. 2023

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Numerous cathepsin B inhibitors have been developed and are under investigation as potential cancer treatments. They have been evaluated for their ability to inhibit cathepsin B activity and reduce tumor growth. However, they have shown critical limitations, including low anticancer efficacy and high toxicity, due to their low selectivity and delivery problems. In this study, we developed a novel peptide and drug conjugate (PDC)-based cathepsin B inhibitor using cathepsin-B-specific peptide (RR) and bile acid (BA). Interestingly, this RR and BA conjugate (RR–BA) was able to self-assemble in an aqueous solution, and as a result, it formed stable nanoparticles. The nano-sized RR–BA conjugate showed significant cathepsin B inhibitory effects and anticancer effects against mouse colorectal cancer (CT26) cells. Its therapeutic effect and low toxicity were also confirmed in CT26 tumor-bearing mice after intravenous injection. Therefore, based on these results, the RR–BA conjugate could be developed as an effective anticancer drug candidate for inhibiting cathepsin B in anticancer therapy.

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“…Cathepsin B is a cysteine protease overexpressed in many cancer cells, including brain cancer cells, and has been exploited in several anti-cancer treatments. [22] To the best of our knowledge, there are very few examples of NIRÀ I organic PS that could be adapted for selective decaging in tissue microenvironments displaying high cathepsin activity. [5] The molecular design of our hCatB-activatable PDT agents included four distinct chemical moieties, namely 1) GlyÀ PheÀ LeuÀ Gly or ValÀ Cit as hCatB-cleavable peptide substrates, [23] 2) the self-immolative 4-aminobenzyl alcohol linker, [24] 3) the Se-bridged hemicyanine PS connected to the linker through the phenol group, and 4) biocompatible moieties to enhance water solubility (i.e., sulfonate groups, PEG or carboxylate-containing units) (Figure 3a).…”

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confidence: 99%

Enzyme‐Activatable Near‐Infrared Hemicyanines as Modular Scaffolds for in vivo Photodynamic Therapy

Cheng,

Benson,

Mendive‐Tapia

et al. 2024

Angewandte Chemie

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Photodynamic therapy is an anti‐cancer treatment that requires illumination of photosensitizers to induce local cell death. Current near‐infrared organic photosensitizers are built from large and non‐modular structures that cannot be tuned to improve safety and minimize off‐target toxicity. This work describes a novel chemical platform to generate enzyme‐activatable near‐infrared photosensitizers. We optimized the Se‐bridged hemicyanine scaffold to include caging groups and biocompatible moieties, and generated cathepsin‐triggered photosensitizers for effective ablation of human glioblastoma cells. Furthermore, we demonstrated that enzyme‐activatable Se‐bridged hemicyanines are effective photosensitizers for the safe ablation of microtumors in vivo, creating new avenues in the chemical design of targeted anti‐cancer photodynamic therapy agents.

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Cathepsin B as a target in cancer therapy and imaging

Abstract: Cysteine cathepsins are important proteases that play important roles in physiological and pathological processes and have the potential to be a candidate target for disease diagnosis and treatment. Among the...

Cited by 5 publications

References 106 publications

Role of Cathepsin B Expression in Oral Squamous Cell Carcinoma: A Comprehensive Review

Role of Cathepsin B Expression in Oral Squamous Cell Carcinoma: A Comprehensive Review

Development of a Peptide-Based Nano-Sized Cathepsin B Inhibitor for Anticancer Therapy

Enzyme‐Activatable Near‐Infrared Hemicyanines as Modular Scaffolds for in vivo Photodynamic Therapy

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