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Development of Organoids from Mouse Pituitary as In Vitro Model to Explore Pituitary Stem Cell Biology
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Ceritinib inhibits growth and ACTH production of PitNETs: Insights from patient-derived organoids

Haoying Yu1, Tingcheng Zhang2, Jiaqian Chen2

  • 1Department of Neurosurgery, Institute of Brain Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Pharmacy, Shenzhen Qianhai Taikang Hospital, Shenzhen, Guangdong 518000, China.

Pharmacological Research
|October 13, 2025
PubMed

Insights

Ceritinib shows promise for treating Cushing's disease (CD), a rare condition. This drug effectively reduced tumor growth and ACTH production in preclinical models, offering a potential new therapy for pituitary neuroendocrine tumors.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Cushing's disease (CD), caused by ACTH-secreting pituitary neuroendocrine tumors (PitNETs), lacks effective pharmacological treatments.
  • Preclinical research models for drug development in CD are limited.

Purpose of the Study:

  • To establish a patient-derived organoid (PDO) model for screening therapeutic agents for CD.
  • To identify effective tyrosine kinase inhibitors for CD treatment.

Main Methods:

  • Development of a patient-derived organoid (PDO) model for pituitary neuroendocrine tumors (PitNETs).
  • Screening of tyrosine kinase inhibitors using the PDO model.
  • In vitro and in vivo validation of Ceritinib efficacy.
  • Multi-omics analyses to elucidate the mechanism of action.

Main Results:

  • Ceritinib demonstrated potent and consistent efficacy in suppressing tumor growth and ACTH production across patient-derived organoids and a xenograft mouse model.
  • Ceritinib inhibits phosphorylation within the PI3K-Akt signaling pathway, with Akt1 identified as a key mediator.
  • Akt1 knockdown attenuated Ceritinib's suppressive effects, and Akt1-mediated regulation of ACTH occurs via Nur77.

Conclusions:

  • Ceritinib is a promising therapeutic candidate for Cushing's disease, effectively suppressing tumor growth and ACTH production.
  • The established PDO model serves as a valuable platform for preclinical drug screening in CD.
  • Targeting the Akt1/Nur77 axis offers a potential therapeutic strategy for CD.
Keywords:
Akt1CeritinibCushing’s diseaseNur77PI3K-Akt pathwayPatient-derived organoidPitNETsTherapeutic target

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