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Targeting of human cancer stem cells predicts efficacy and toxicity of FDA-approved oncology drugs.
Vojnits, Kinga; Feng, Zhuohang; Johnson, Paige; Porras, Deanna; Manocha, Ekta; Vandersluis, Sean; Pfammatter, Sibylle; Thibault, Pierre; Bhatia, Mick.
Afiliación
  • Vojnits K; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
  • Feng Z; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
  • Johnson P; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
  • Porras D; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
  • Manocha E; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
  • Vandersluis S; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
  • Pfammatter S; Department of Chemistry and Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada.
  • Thibault P; Department of Chemistry and Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada.
  • Bhatia M; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada. Electronic address: mbhatia@mcmaster.ca.
Cancer Lett ; 599: 217108, 2024 Sep 01.
Article en En | MEDLINE | ID: mdl-38986735
ABSTRACT
Cancer remains the leading cause of death worldwide with approved oncology drugs continuing to have heterogenous patient responses and accompanied adverse effects (AEs) that limits effectiveness. Here, we examined >100 FDA-approved oncology drugs in the context of stemness using a surrogate model of transformed human pluripotent cancer stem cells (CSCs) vs. healthy stem cells (hSCs) capable of distinguishing abnormal self-renewal and differentiation. Although a proportion of these drugs had no effects (inactive), a larger portion affected CSCs (active), and a unique subset preferentially affected CSCs over hSCs (selective). Single cell gene expression and protein profiling of each drug's FDA recognized target provided a molecular correlation of responses in CSCs vs. hSCs. Uniquely, drugs selective for CSCs demonstrated clinical efficacy, measured by overall survival, and reduced AEs. Our findings reveal that while unintentional, half of anticancer drugs are active against CSCs and associated with improved clinical outcomes. Based on these findings, we suggest ability to target CSC targeting should be included as a property of early onco-therapeutic development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Aprobación de Drogas / Antineoplásicos Límite: Humans País/Región como asunto: America do norte Idioma: En Revista: Cancer Lett Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Aprobación de Drogas / Antineoplásicos Límite: Humans País/Región como asunto: America do norte Idioma: En Revista: Cancer Lett Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Irlanda