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CMCC 1247

Methods to predict, prevent and revert resistance to taxoid compounds

Inventors: Bruce Zetter, Sabarni Chatterjee

Invention Types: Diagnostic/Prognostic, Therapeutics

Research Areas: Oncology/Hematology

Keywords: Biomarker, Method of Use

Related Cases: 2258

For More Information Contact:  Wong, Adrienne

 

Invention Description:

Taxoid compounds such as paclitaxel (Taxol®) and docetaxel (Taxotere®) are widely used treatments for aggressive malignancies of the breast, lung, prostate and ovaries. As with other traditional chemotherapeutic agents, resistance to taxoids is common and limits treatment success. Using a proteomics approach, Drs. Zetter and Chatterjee have found elevated levels of prohibitin, a mitochondrial chaperone protein known to regulate cell survival and growth, on the surface of paclitaxel-resistant lung cancer cells and uterine sarcoma cells versus parental cells. Moreover, knockdown of prohibitin in these paclitaxel-resistant cells sensitized them to drug treatment with such agents as etoposide, doxyrubicin, and cisplatin.

Paclitaxel has been used extensively to treat lung, prostate, ovarian and breast cancers but drug resistance limits the clinical usefulness of this drug. For example, no objective response with taxane-based regiments is observed in 40-80% of women with metastatic breast cancer (primary resistance); all taxane responders eventually relapse after 6-12 months (secondary resistance).

Applications:

Prohibitin as a new therapeutic target to delay and reverse resistance to taxoids and as a biomarker for taxane resistance.

Competitive Advantages:

• Prohibitin's involvement in drug resistance opens up a new avenue to modulate chemotherapeutic drug response and sensitize cancer cells to drug treatment
• Prohibitin could be used as a biomarker for selecting patients likely to respond to taxane therapy. In addition, proteins that inhibit prohibitin or mimic its action may be an effective strategy for modulating the response to paclitaxel or docetaxel
• The presence of prohibitin on the cell surface of taxane-resistant cancer cells could be used as a means to specifically target and deliver alternative, non-taxane based chemotherapeutic agents

Business Opportunity:

Collaboration and licensing opportunities available

Key Publications: Patel et al., 2010. Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells. PNAS 107(6): 2503-2508

Xu Y, et al., 2016. Prohibitin 1 regulates tumor cell apoptosis via the interaction with X-linked inhibitor of apoptosis protein. J Mol Cell Biol 8(3):282-285

Related Publications: US Issued #8,148,086, EPO Issued #1948213

IPStatus: Patented