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Activity of roniciclib in medullary thyroid cancer

Shu-Fu Lin1, Jen-Der Lin1, Chuen Hsueh2

  • 1Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.

Oncotarget
|July 3, 2018
PubMed

Insights

Roniciclib, a cyclin-dependent kinase inhibitor, effectively reduced medullary thyroid cancer cell growth and tumor progression in preclinical models. Combination therapy with sorafenib showed enhanced efficacy without observed toxicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Altered cyclin-dependent kinase (CDK) activity is a hallmark of human malignancies.
  • CDKs regulating cell cycle progression represent potential therapeutic targets for cancer treatment.

Purpose of the Study:

  • To investigate the therapeutic effects of roniciclib, a CDK inhibitor, in medullary thyroid cancer (MTC).
  • To evaluate the efficacy of roniciclib, alone and in combination with sorafenib, in preclinical MTC models.

Main Methods:

  • In vitro assessment of roniciclib's effects on MTC cell proliferation, apoptosis (caspase-3 activity), and cell cycle progression.
  • In vivo evaluation of roniciclib's efficacy on MTC xenograft tumor growth.
  • Assessment of combination therapy with roniciclib and sorafenib in MTC xenografts.

Main Results:

  • Roniciclib demonstrated dose-dependent inhibition of MTC cell proliferation.
  • Roniciclib induced apoptosis and G2 phase cell cycle arrest in MTC cells.
  • Roniciclib treatment significantly retarded MTC xenograft tumor growth.
  • Combination therapy with roniciclib and sorafenib was more effective than monotherapy.
  • No significant morbidity was observed in animals treated with roniciclib or combination therapy.

Conclusions:

  • Roniciclib exhibits significant anti-cancer activity against medullary thyroid cancer in vitro and in vivo.
  • Combination of roniciclib with sorafenib enhances therapeutic efficacy in MTC models.
  • These findings support the clinical investigation of roniciclib for medullary thyroid cancer treatment.
Keywords:
cyclin-dependent kinasemedullary thyroid cancerroniciclib

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