Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review DOI Open Access
Romana Masnikosa, Zorica Cvetković, David Pirić

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11384 - 11384

Published: Oct. 23, 2024

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline tumor biology behind actual potential drug targets address challenges drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-drug conjugates, chimeric antigen receptors, bispecific antibodies T-cell engagers, immune checkpoint inhibitors. Candidate drugs explored in ongoing trials diverse toxicity issues refractoriness drugs. According literature DLBCL, promise for new therapeutic lies epigenetic alterations, receptor NF-κB pathways. present putative hiding lipid pathways, ferroptosis, gut microbiome that could be used addition immuno-chemotherapy improve general health status patients, thus increasing chance being cured. It may time devote more effort exploring metabolism discover novel druggable targets. We also performed bibliometric knowledge-map analysis published from 2014-2023.

Language: Английский

Innovative payloads for ADCs in cancer treatment: moving beyond the selective delivery of chemotherapy DOI Creative Commons
Domenico Izzo, Liliana Ascione, Lorenzo Guidi

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 1, 2025

Antibody–drug conjugates (ADCs) have emerged as a transformative approach in cancer therapy by enhancing tumor targeting and minimizing systemic toxicity compared to traditional chemotherapy. Initially developed with chemotherapy agents payloads, ADCs now incorporated alternative such immune-stimulating agents, natural toxins, radionuclides, improve therapeutic efficacy specificity. A significant advancement ADC technology is the integration of Proteolysis Targeting Chimeras (PROTACs), which enable precise degradation cellular targets involved tumorigenesis. This strategy enhances specificity precision therapies, addressing key mechanisms cell survival. Moreover, incorporating radioactive isotopes into an emerging aimed at further improving outcomes. By delivering localized radiation, this offers potential enhance treatment expand arsenal. Despite these innovations, challenges remain, including dysregulated immune activation, severe adverse effects, intrinsic immunogenicity some agents. These issues highlight ongoing need for optimization therapy. review summarizes latest developments technology, focusing on novel PROTAC integration, combining other modalities refine patient

Language: Английский

Citations

3
Exploring the clinical trials, regulatory insights, and challenges of PROTACs in oncology DOI

M Sowndharya,

Ramesh Joga,

Kajal Gandhi

et al.

Seminars in Oncology, Journal Year: 2025, Volume and Issue: 52(2), P. 152339 - 152339

Published: April 1, 2025

Language: Английский

Citations

0
A high throughput compatible workflow for the biochemical identification and characterisation of molecular glues DOI Creative Commons
Ryan Guilbert,

Maxime Couturier,

Yuanyuan Si

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108526 - 108526

Published: April 1, 2025

Molecular glues are an emerging modality which induces or enhances interaction between two proteins. can target proteins via proximity-induced degradation sequestration and can, therefore, provide opportunities for therapeutic intervention to targets that cannot be modulated by traditional small molecule approaches. Due their modest molecular weight, may not encounter the bioavailability issues associated with PROTACs. Characterisation of in hit finding optimisation settings challenging, as both affinity glue protein resulting improvement interest need assessed parallel. Here, we propose validate a workflow derive key parameters from classic concentration response experiment. Furthermore, method rational determination optimum biochemical assay conditions identify characterise glues.

Language: Английский

Citations

0
Discovery of ERD-1233 as a Potent and Orally Efficacious Estrogen Receptor PROTAC Degrader for the Treatment of ER+ Human Breast Cancer DOI
Ranjan Kumar Acharyya, Rohan Kalyan Rej, Biao Hu

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(21), P. 19010 - 19037

Published: Nov. 1, 2024

Despite the development of highly effective therapies for treatment estrogen receptor α (ERα)-positive human breast cancer, clinical resistance to current requires novel therapeutic strategies. Herein, we report discovery ERD-1233 as a potent and orally efficacious ERα degrader designed using PROTAC technology. was developed based on Lasofoxifene ER binding moiety cereblon ligand through extensive optimization linker. potently effectively reduces protein in vitro achieves excellent oral bioavailability mice rats. Oral administration ER+ tumors tumor regression wild-type MCF-7 xenograft model strong growth inhibition ESR1Y537S mutated mice. Our data demonstrate that is promising evaluation new therapy cancer.

Language: Английский

Citations

3
Discovery of a Potent, selective and orally bioavailable CDK9 degrader for targeting transcription regulation in Triple-Negative breast cancer DOI

Hui-Jun Nie,

Benfu Li,

Jingya Sun

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107876 - 107876

Published: Oct. 9, 2024

Language: Английский

Citations

2
To homeostasis and beyond! Recent advances in the medicinal chemistry of heterobifunctional derivatives DOI

Diana Castagna,

Benoit Gourdet,

Roland Hjerpe

et al.

Progress in medicinal chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 61 - 160

Published: Jan. 1, 2024

Language: Английский

Citations

1
Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review DOI Open Access
Romana Masnikosa, Zorica Cvetković, David Pirić

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11384 - 11384

Published: Oct. 23, 2024

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline tumor biology behind actual potential drug targets address challenges drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-drug conjugates, chimeric antigen receptors, bispecific antibodies T-cell engagers, immune checkpoint inhibitors. Candidate drugs explored in ongoing trials diverse toxicity issues refractoriness drugs. According literature DLBCL, promise for new therapeutic lies epigenetic alterations, receptor NF-κB pathways. present putative hiding lipid pathways, ferroptosis, gut microbiome that could be used addition immuno-chemotherapy improve general health status patients, thus increasing chance being cured. It may time devote more effort exploring metabolism discover novel druggable targets. We also performed bibliometric knowledge-map analysis published from 2014-2023.

Language: Английский

Citations

1