Small molecule inhibitor of CHFR to increase taxane efficacy in cancer treatment.
Combination treatment, potentially effective against cancers resistant to taxane treatment.
Approximately 400,000 Americans are living with lung cancer and over 200,000 more are diagnosed each year. Microtubular-targeted chemotherapy agents such as taxanes are among the most widely prescribed first- and second- line chemotherapy choices for patients with the most common malignancies including lung-, breast-, and prostate cancer. Unfortunately, primary resistance to taxanes is a common clinical problem. CHFR protein levels and CHFR promoter methylation are highly predictive of response to the taxane class of chemotherapeutics. Tumors with high CHFR levels and unmethylated promoters are generally significantly more resistant to taxanes. Patients with low CHFR expression or CHFR methylation are more than twice as likely to derive clinical benefit from taxane based chemotherapy.
CHFR protein stability depends on a protein-protein interaction with poly-ADP-ribose polymerase (PARP)-1. Dr. Brandes has developed a novel CHFR inhibitor based on the disruption of the protein-protein interaction of CHFR with PARP-1. This small molecule inhibitor of CHFR may be administered in combination with a mitotic inhibitor such as taxane for increased taxane efficacy in cancer treatment. In combination with docetaxel, the compound significantly decreased tumor size compared to docetaxel alone, demonstrating that pharmacologic targeting of the CHFR/PARP interaction may indeed be a promising strategy to improve taxane sensitivity in lung cancer. This technology may be used to improve the efficacy of cancer treatments.
- In vitro and in vivo data are available.
- Companion diagnostic is available.