ArticleOncology reports2021
In vitro and ex vivo anti‑tumor effect and mechanism of Tucatinib in leukemia stem cells and ABCG2‑overexpressing leukemia cells.
Article in Oncology reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- ATP-Binding Cassette Subfamily G Member 2 in Acute Myeloid Leukemia: A New Molecular Target?Biomedicines · 2024Review
- Drug resistance of hepatoma cells induced by ATP‑binding cassette transporter G2 by reducing intracellular drug concentration.Experimental and therapeutic medicine · 2023Article
- Markers and Reporters to Reveal the Hierarchy in Heterogeneous Cancer Stem Cells.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukemia stem cells (LSCs), which evade standard chemotherapy, may lead to chemoresistance and disease relapse. The overexpression of ATP‑binding cassette subfamily G member 2 (ABCG2) is an important determinant of drug resistance in LSCs and it can serve as a marker for LSCs. Targeting ABCG2 is a potential strategy to selectively treat and eradicate LSCs, and, hence, improve leukemia therapy. Tucatinib (Irbinitinib) is a novel tyrosine kinase inhibitor, targeting ErbB family member HER2, and was approved by the Food and Drug Administration in April 2020, and in Switzerland in May 2020 for the treatment of HER2‑positive breast cancer. In the present study, the results demonstrated that tucatinib significantly improved the efficacy of conventional chemotherapeutic agents in ABCG2‑overexpressing leukemia cells and primary leukemia blast cells, derived from patients with leukemia. In addition, tucatinib markedly decreased the proportion of leukemia stem cell‑like side population (SP) cells. In SP cells, isolated from leukemia cells, the intracellular accumulation of Hoechst 33342, which is an ABCG2 substrate, was significantly elevated by tucatinib. Furthermore, tucatinib notably inhibited the efflux of [3H]‑mitoxantrone and, hence, there was a higher level of [3H]‑mitoxantrone in the HL60/ABCG2 cell line. The result from the ATPase assay revealed that tucatinib may interact with the drug substrate‑binding site and stimulated ATPase activity of ABCG2. However, the protein expression level and cellular location of ABCG2 were not affected by tucatinib treatment. Taken together, these data suggested that tucatinib could sensitize conventional chemotherapeutic agents, in ABCG2‑overexpressing leukemia cells and LSCs, by blocking the pump function of the ABCG2 protein. The present study revealed that combined treatment with tucatinib and conventional cytotoxic agents could be a potential therapeutic strategy in ABCG2‑positive leukemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.