MD Anderson Focuses on Preclinical Findings with Investigational Small Molecule in Medullary Thyroid Cancer


An investigational small molecule called ONC201 alone or in combination with a tyrosine kinase inhibitor (TKI) can reverse RET-mediating signaling through its effect on activating Transcription Factor-4 (ATF4) in patients with medullary thyroid cancer (MTC).

ONC201 was shown to inhibit the kinase activity of RET while increasing the transcription of ATF4 to enhance cell death.  These agent also showed synergy in combination with TKI reports from Targeted Oncology.

Lead investigator Rozita Yarmand, PhD, said “The standard of care for MTC right now is for multi-TKIs, cabozantinib (Cabometyx) and vandetanib (Capresla), but with those drugs, patients experience resistance and their response is partial, so we need novel compounds that have less toxicity with durable response.”

Follow the link below to read an interview with Targeted Oncology.  Yarmand discusses the rational for investigating ONC201 in patients with MTC and the toxicity profile that has been seen with this small molecule in mouse models and in other tumor types.

Lear Research/Investigator

Rozita Yarmand, PhD, MD Anderson