CTSL (Cathepsin L)

USP20 deubiquitinates and stabilizes CTSL. STUB1 promotes CTSL ubiquitination and degradation. USP20 competitively binds to CTSL in competition with STUB1. Targeting USP20 sensitizes cancer cells to cisplatin or paclitaxel.

Moreover, the combination of CTSL inhibitor and docetaxel effectively suppressed tumor growth in vivo...Finally, CTSL mediates chemotherapy resistance by regulating the expression of HGFAC/HGF/Met signaling pathway. Taken together, our findings establish CTSL as a pivotal driver of MDR in NSCLC, highlighting its promise as a therapeutic target to overcome this challenge.

Clinically, high CTSL expression correlates with increased PD-L1, scarce CD8+ T-cell infiltration, and poor prognosis in multiple HNSCC cohorts. Collectively, our data identify CTSL as a key driver of PD-L1-dependent immune evasion through the CTSL-PDK1-AKT axis and highlight CTSL inhibition as a promising therapeutic strategy and predictive biomarker for PD-1/PD-L1 blockade in HNSCC.

Mitoxantrone, a promising inducer, is encapsulated in platelet membrane-hybridized liposomes to enhance targeted delivery and therapeutic efficacy...This activated Caspase8 and the NLRP3 inflammasome, leading to GSDMC cleavage and initiating pyroptosis. Collectively, this study provides an innovative pyroptosis therapy strategy combining physical treatment and chemotherapy for BLBC and other refractory diseases.

Herein, we present FR-DCO, a cathepsin L (CTSL)-activatable fluorescent probe, engineered for targeted imaging of doxorubicin-resistant breast cancer cells (MCF-7/ADR)...Notably, dual-tumor xenograft models confirmed precise discrimination of MCF-7/ADR tumors from 4T1 tumors, highlighting the spatial resolution of the probe. This work not only provides a molecular tool for spatiotemporal resistance monitoring, but also establishes a modular design paradigm for enzyme-responsive probes targeting tumor microenvironment biomarkers, advancing precision oncology strategies.

Notably, T-DXd cytotoxicity also upregulates tumor CD47 expression, dampening immune activation. Combining T-DXd with CD47 checkpoint blockade significantly enhances anti-tumor immune responses in a HER2-transgenic BC mouse model, while also inducing durable CD8+ T cell memory to prevent tumor recurrence after therapy cessation.

Our study demonstrated that HQI, particularly its active component CG, holds potential as a therapeutic agent for osteosarcoma. The primary mechanism underlying its anti-osteosarcoma effects involves modulating the immune response and targeting CTSL. These findings provide a scientific basis for the development of HQI as a novel immunomodulatory therapy for osteosarcoma.

We found that CTSL upregulates autophagy in laryngeal cancer cells by activating the IL6-JAK-STAT3 signalling pathway. By taking into account the autophagy-regulating role of CTSL, the clinical predictive ability of CTSL in HNSC can be enhanced.

In consideration of our findings, tumor-associated macrophage-derived CTSL is an important factor that promotes the metastasis and invasion of gastric cancer cells, and the targeting of CTSL may potentially improve the prognosis of patients with gastric cancer with peritoneal metastasis.

This study highlights the crucial role of CTSL as a prognostic biomarker in LUAD. This combined multicenter and omics-based analysis provides comprehensive insights into the biological role of CTSL, supporting its potential as a target for therapeutic intervention and a marker for prognosis in patients with LUAD.

SnuCalCpI15 was localized intracellularly in MDA-MB-231 breast cancer cells and suppressed tumor cell migration and invasion. These results demonstrate the potential of SnuCalCpI15 as a novel agent to prevent breast cancer metastasis.

Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.