The NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program’s establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.
NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.
This feature highlights an NCCN study funded through the grant mechanism.
Refractory Hormone Receptor–Positive Breast Cancer: A Role for Estrogen Receptor β
Principal Investigator: Matthew Cherian, MBBS
Condition: Breast cancer – preclinical
Institution: The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute
In the development of resistance to first-line endocrine and CDK4/6 inhibitors, the greatest challenge in the management of estrogen receptor α–positive breast cancer is maintained by diverse and intersecting signaling pathways, precluding the development of therapies that target a single resistance factor. Dr. Cherian’s data demonstrate that activation of a second estrogen receptor, estrogen receptor β (ERβ), leads to transcriptional upregulation of key tumor suppressors known as the FOXO transcription factors. Dr. Cherian proposes a novel therapeutic strategy that will reactivate FOXO transcription factors using combinations of a highly specific, ERβ agonist, LY500307, and abemaciclib to concurrently counter the multiple mechanisms of endocrine and CDK4/6 resistance in breast cancer. This is an in vivo, retrospective study.
Aim 1: to counter endocrine resistance in preclinical models of breast cancer with ERβ agonist–CDK4/6 inhibitor combinations
Aim 2: to override CDK4/6 inhibitor resistance in preclinical models of breast cancer with ERβ agonist–CDK4/6 inhibitor combinations