A5078294222- Tuberculosis Research and Epidemiology
- Protein Degradation and Inhibitors
- Diagnosis and treatment of tuberculosis
- RNA and protein synthesis mechanisms
- Melanoma and MAPK Pathways
- Cancer-related molecular mechanisms research
- Mycobacterium research and diagnosis
- Cancer Immunotherapy and Biomarkers
- Nanoplatforms for cancer theranostics
- Herpesvirus Infections and Treatments
- Endoplasmic Reticulum Stress and Disease
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Immunotherapy and Immune Responses
VIB-KU Leuven Center for Cancer Biology
2020-2023
KU Leuven
2021
The ability to adapt environmental stress, including therapeutic insult, contributes tumor evolution and drug resistance. In suboptimal conditions, the integrated stress response (ISR) promotes survival by dampening cytosolic translation. We show that ISR-dependent also relies on a concomitant up-regulation of mitochondrial protein synthesis, vulnerability can be exploited using mitoribosome-targeting antibiotics. Accordingly, such agents sensitized MAPK inhibition, thus preventing...
Abstract Although immune checkpoint blockade (ICB) has revolutionized cancer treatment, resistance mechanisms limit its clinical benefit. Here we characterise LISRR , a cancer-specific lncRNA highly expressed in melanoma patients refractory to ICB. In cells undergoing (therapeutic) stress, recruits DAZAP1 (Deleted AZoospermia Associated Protein 1) polysomes and drives the assembly of subset ribosomes at endoplasmic reticulum, directing synthesis an immunosuppressive translatome. This...
There is currently no consensus to determine which advanced melanoma patients will benefit from immunotherapy, highlighting the critical need identify early-response biomarkers immune checkpoint inhibitors. The aim of this work was evaluate in vivo metabolic spectroscopy using hyperpolarized (HP) 13C-pyruvate and 13C-glucose assess early response anti-PD1 therapy YUMMER1.7 syngeneic model. xenografts showed a significant tumor growth delay when treated with two cycles an antibody compared...
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Summary Therapy resistance remains a major clinical challenge for the management of metastatic melanoma. Here we show that activation Integrated Stress Response (ISR), which is common in drug-tolerant and resistant melanoma, promotes selective synthesis mitochondrial proteins cytosol. Since translation adapts to influx nuclear-encoded proteins, ISR indirectly enhances makes these cells highly vulnerable inhibitors. Treatment melanoma with mitoribosome-targeting antibiotics, induces...