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Cited by 40Neuroblastoma Research and TreatmentsPI3K/AKT/mTOR signaling in cancerGlioma Diagnosis and Treatment

Anti‐tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL‐302 in neuroblastoma

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Mohlin, Sofie, Hansson, Karin, Radke, Katarzyna, Martinez, Sonia, Blanco‐Apiricio, Carmen, Garcia‐Ruiz, Cristian, Welinder, Charlotte, Esfandyari, Javanshir +4 more·2019·EMBO Molecular Medicine
DOI 10.15252/emmm.201810058PMC PMC6685085
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Abstract

The PI3K pathway is a major driver of cancer progression. However, clinical resistance to PI3K inhibition is common. IBL-302 is a novel highly specific triple PIM, PI3K, and mTOR inhibitor. Screening IBL-302 in over 700 cell lines representing 47 tumor types identified neuroblastoma as a strong candidate for PIM/PI3K/mTOR inhibition. IBL-302 was more effective than single PI3K inhibition in vitro, and IBL-302 treatment of neuroblastoma patient-derived xenograft (PDX) cells induced apoptosis, differentiated tumor cells, and decreased N-Myc protein levels. IBL-302 further enhanced the effect of the common cytotoxic chemotherapies cisplatin, doxorubicin, and etoposide. Global genome, proteome, and phospho-proteome analyses identified crucial biological processes, including cell motility and apoptosis, targeted by IBL-302 treatment. While IBL-302 treatment alone reduced tumor growth in vivo, combination therapy with low-dose cisplatin inhibited neuroblastoma PDX growth. Complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition has the potential to improve clinical outcomes and reduce severe late effects in children with high-risk neuroblastoma.

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  • Current treatment strategies for ESCC primarily include surgery, radiotherapy, and chemotherapy.

    “Current treatment strategies for ESCC primarily include surgery, radiotherapy, and chemotherapy.27,28”

    From Macrophage efferocytosis mediated by the TP63-RAC2 pathway promotes immunosuppressive remodeling in esophageal cancer (2026) · cites this paper as [28]

    The Introduction lists surgery, radiotherapy, and chemotherapy among current treatments for neuroblastoma. It does not address treatment strategies for ESCC, so the claim’s disease-specific attribution is unsupported. (LLM, conf=0.87)

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Sorted by citations

Authors
Mohlin, S., Hansson, K., Radke, K., Martinez, S., Blanco‐Apiricio, C., Garcia‐Ruiz, C., Welinder, C., Esfandyari, J., O'Neill, M., Pastor, J., von Stedingk, K., & Bexell, D.
Affiliations
Lund University (SE)
Corresponding author
  • Mohlin, Sofie
  • Bexell, Daniel
ORCID
Venue
EMBO Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2019-07-16
Volume
11
Issue
8
Pages
e10058-e10058
ISSN
  • 1757-4676 (ISSN-L)
  • 1757-4684
DOI
10.15252/emmm.201810058
PMC
PMC6685085
OpenAlex
W2961239351
Cited by
40
References
2
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 10 · 2021: 10 · 2020: 10 · 2019: 1 · 2018: 1
FWCI
5.24
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • EMBO Molecular Medicine (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Swedish Research Council
  • Cancerfonden
  • Barncancerfonden
  • Region Skåne
  • Research Funds of Skåne University Hospital
  • Mary Bevé Foundation
  • Magnus Bergvalls stiftelse
  • Thelma Zoéga Foundation
  • Hans von Kantzow Foundation
  • Crafoord Foundation
  • Åke Wiberg Foundation
  • Jeanssons Stiftelser
  • Ollie och Elof Ericssons stiftelser
  • Berth von Kantzows stiftelse
  • Royal Physiographic Society of Lund
  • Spanish Ministry of Health and Social Policy (ADE08/90038)
  • Spanish Ministry of Science and Innovation (CIT‐090000‐2008‐14)
Topics
  • Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
Keywords
PIM kinases, PI3K inhibition, mTOR inhibition, neuroblastoma, PI3K signaling, MYCN, apoptosis, tumor differentiation, cisplatin combination therapy, patient-derived xenografts, chemoresistance, phosphoproteomics, cell motility, childhood cancer
MeSH terms
N-Myc Proto-Oncogene Protein, Phosphoinositide-3 Kinase Inhibitors, Animals, Antineoplastic Combined Chemotherapy Protocols, Cell Differentiation, Cell Movement, Female, Humans, Mice, Nude, Neuroblastoma, Proto-Oncogene Proteins, Pyridines, Pyrimidines, Thiophenes, Signal Transduction, Apoptosis, Protein Serine-Threonine Kinases, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Phosphatidylinositol 3-Kinase, TOR Serine-Threonine Kinases

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