GBM is the most aggressive form of brain cancer. The current standard of care against GBM is a combination of surgery, chemotherapy and radiotherapy. However, after standard treatment, the cancer usually recurs – emphasizing a need for new targets and better alternatives. A promising target is cyclin-dependent kinase 5 (CDK5), the hyperactivity of which has been shown to have a role in cancer progression.
TP5/TFP5, a small peptide inhibitor against CDK5, was developed at the National Institutes of Health and modified to increase its passage through the blood brain barrier. Researchers at the NCI and NINDS demonstrated that TP5 decreases cell viability and increases programmed cell death in GBM and CRC cell lines with aberrant CDK5 activity. TP5 was found to impair DNA repair by inhibiting CDK5 and acted additively and synergistically with DNA-damaging agents (e.g. temozolomide, irinotecan, irradiation) used in treatment of GBM and colon carcinoma. TP5 decreased the tumor volume and increased the overall survival of orthotopic glioblastoma mouse models.
The Neuro-Oncology Branch is seeking statements of capability or interest from parties interested in licensing this invention to further develop, evaluate, or commercialize TP5 for novel treatment of GBM and/or other cancers with aberrant CDK5 expression.
- Treatment of GBM and other brain tumors with aberrant CDK5 expression
- Treatment of other cancers with aberrant CDK5 expression, including CRC and lung cancer
- The GBM market is expected to grow to >U$1B at a compound annual growth rate (CAGR) of 7.5%
- The CRC market has risen to >US$8B at a CAGR of 3%
- Decreases the tumor volume and the proliferation rate of GBM in mouse models
- Can cross the blood-brain barrier, overcoming a major obstacle for the therapeutic agent development for GBM
- Decreases the tumor volume in CRC mouse models
- Additive as well as synergistic with the current standard of care
- CDK5 expression and activity are deregulated in cancer cells; because CDK5 is not a tumor-associated mutation, the role of CDK5 in cancer has been underappreciated until recently – meaning less competition
- Roscovitine, another CDK inhibitor, was shown to delay resistance to temozolomide – the only approved drug for GBM
Tabouret E, et al. TP5, a peptide inhibitor of aberrant and hyperactive CDK5/p25: a novel therapeutic approach against glioblastoma. [Oxford Academic]
Binukumar BK, et al. TFP5/TP5 peptide provides neuroprotection in the MPTP model of Parkinson’s disease. [PMID: 27335538]
Binukumar BK, et al. Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease. [PMID: 26399293]
- PCT: PCT Application Number US2019/061251, Filed 13 Nov 2019, Filed 14 Nov 2018