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Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
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Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

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ONC201 (Dordaviprone) Induces Integrated Stress Response and Death in Cervical Cancer Cells

Sneha O Pathak1, Sonal M Manohar1

  • 1Department of Biological Sciences, Sunandan Divatia of School of Science, SVKM's NMIMS (Deemed-to-be) University, Vile Parle (West), Mumbai 400056, India.

Biomolecules
|April 30, 2025
PubMed

Insights

ONC201 demonstrates significant anticancer effects against cervical cancer cells by inducing apoptosis and cell cycle arrest. This drug shows promise as a novel therapeutic agent, even exhibiting synergistic effects with standard treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cervical cancer remains a significant global health challenge for women.
  • Current systemic chemotherapy for advanced cervical cancer has limited efficacy due to toxicity and drug resistance.
  • ONC201, a TRAIL and cIpP agonist, is under investigation for various cancers.

Purpose of the Study:

  • To evaluate the anticancer potential of ONC201 in human papillomavirus (HPV)-positive cervical cancer cell lines.
  • To elucidate the mechanism of action of ONC201 in cervical cancer.
  • To assess the synergistic effects of ONC201 in combination with standard chemotherapeutic agents.

Main Methods:

  • Investigated ONC201's cytotoxicity and clonogenic inhibition in cervical cancer cell lines (HeLa and SiHa).
  • Assessed the induction of integrated stress response, cell cycle arrest (S/G2-M), and apoptosis.
  • Monitored the expression of key targets including TRAIL, DR5, cIpP, BNIP3, and Beclin-1.
  • Evaluated the synergistic effects of ONC201 in combination with standard drugs.

Main Results:

  • ONC201 significantly reduced cervical cancer cell viability and clonogenic potential.
  • The drug induced integrated stress response, S/G2-M cell cycle arrest, and apoptosis.
  • TRAIL, DR5, and cIpP upregulation was observed in HeLa cells but not SiHa cells.
  • Expression of autophagy-related proteins BNIP3 and Beclin-1 increased with ONC201 treatment.
  • ONC201 demonstrated synergistic activity when combined with standard chemotherapeutic agents.

Conclusions:

  • ONC201 exhibits potent anticancer activity against HPV-positive cervical cancer cells.
  • The drug's mechanism involves inducing apoptosis and cell cycle arrest, with differential target modulation.
  • ONC201 shows potential as a novel therapeutic agent for cervical cancer, particularly in combination therapy.
Keywords:
ONC201TIC10apoptosiscervical cancerdordaviproneintegrated stress responsesmall molecule

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