Satraplatin Demonstrates High Cytotoxic Activity Against Genetically Defined Lymphoid Malignancies.


Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Apr 2022
Historique:
received: 08 01 2022
revised: 14 02 2022
accepted: 16 02 2022
entrez: 29 3 2022
pubmed: 30 3 2022
medline: 5 4 2022
Statut: ppublish

Résumé

Satraplatin is an oral platinum analog with proven clinical efficacy and a more favorable toxicity profile, although with increased hematotoxicity, when compared to cisplatin. Hence, we carried out a systematic biomarker analysis to identify hematological malignancies with high susceptibility to satraplatin. Half-maximal inhibitory concentrations (IC Satraplatin was significantly more active against hematological malignancies compared to solid organ cancer. In addition, satraplatin showed a significantly more potent antiproliferative activity compared to cisplatin in most lymphoma cell lines achieving sub micromolar IC Satraplatin demonstrated a high cytotoxic activity in genetically well-defined hematological malignancies which is distinct from that of cisplatin. MTAP deficiency was identified as biomarker of enhanced satraplatin efficacy in hematological cancer-derived cell lines. These data in combination with the lipophilicity of satraplatin provide the rationale for targeting specific lymphatic entities such as primary central nervous system lymphoma and cutaneous T-cell lymphoma to improve clinical outcome.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
Satraplatin is an oral platinum analog with proven clinical efficacy and a more favorable toxicity profile, although with increased hematotoxicity, when compared to cisplatin. Hence, we carried out a systematic biomarker analysis to identify hematological malignancies with high susceptibility to satraplatin.
MATERIALS AND METHODS METHODS
Half-maximal inhibitory concentrations (IC
RESULTS RESULTS
Satraplatin was significantly more active against hematological malignancies compared to solid organ cancer. In addition, satraplatin showed a significantly more potent antiproliferative activity compared to cisplatin in most lymphoma cell lines achieving sub micromolar IC
CONCLUSION CONCLUSIONS
Satraplatin demonstrated a high cytotoxic activity in genetically well-defined hematological malignancies which is distinct from that of cisplatin. MTAP deficiency was identified as biomarker of enhanced satraplatin efficacy in hematological cancer-derived cell lines. These data in combination with the lipophilicity of satraplatin provide the rationale for targeting specific lymphatic entities such as primary central nervous system lymphoma and cutaneous T-cell lymphoma to improve clinical outcome.

Identifiants

pubmed: 35347000
pii: 42/4/1821
doi: 10.21873/anticanres.15658
doi:

Substances chimiques

Antineoplastic Agents 0
Organoplatinum Compounds 0
satraplatin 8D7B37T28G
Cisplatin Q20Q21Q62J

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1821-1832

Informations de copyright

Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Thilo Zander (T)

Dayton Therapeutics AG, Steinhausen, Switzerland.

Jia Xue (J)

Crown Biosciences Inc., Jiangsu, P.R. China.

Gabriel Markson (G)

Dayton Therapeutics AG, Steinhausen, Switzerland.

Felix Dahm (F)

Dayton Therapeutics AG, Steinhausen, Switzerland.

Christoph Renner (C)

Dayton Therapeutics AG, Steinhausen, Switzerland; christoph.renner@daytontherapeutics.com.

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Classifications MeSH