miRNA-135a to detect and reverse taxane resistance in tumor cells
Inventors: Bruce Zetter, Ivy Chung, Amy Holleman
Invention Types: Diagnostic/Prognostic, Therapeutics
Research Areas: Oncology/Hematology, Personalized Medicine
Keywords: Biomarker, Cell Line, Method of Use
Related Cases: 1247For More Information Contact: Ives, Catherine L.
Dr. Zetter's lab screened taxane-resistant tumor cells and taxane-sensitive cells for differences in miRNA expression. They identified miR-135a as being upregulated in resistant tumor cells relative to sensitive cells. Cancer types tested included prostate cancer, breast cancer and uterine carcinoma.
Additionally, paclitaxel-resistant tumors were selected by inoculating mice with A549 lung cancer cells and treating the animals 3 times weekly with paclitaxel for 120 days. Tumors became resistant and continued to grow in the presence of paclitaxel. These in vivo-derived paclitaxel resistant tumors showed increased levels of miR-135a, confirming its importance in a model that is similar to that found in clinical practice in human patients where resistance arises over time. Additionally, the tumor cells remain exposed to the tumor microenvironment.
The researchers found that the inhibition of miR-135a with a specific inhibitor (antagomir) reversed the resistance to Paclitaxel in resistant lung cancer cells, showing that miR-135a is essential to taxane resistance in this model.
• Inhibition of miR-135a could reverse taxane resistance in human cancer patients that are resistant to paclitaxel treatment. These patients would then be responsive to taxane therapy for longer time periods.||
• miR-135a could be used as a biomarker for taxane-resistance in patient tissues or fluids. Cells, tissues or fluids with increased levels of miR-135a relative to taxane-sensitive patient standards, would be determined to be at greater risk to have or develop resistance to such drugs.||
• Currently, patients who are or who become resistant to taxanes have limited treatment options and have a short life expectancy. |
• Despite their widespread use, the clinical effectiveness of taxanes is limited by the emergence of taxane-resistant cancer cells, which ultimately leads to relapse and poor prognosis.|
• There is a distinct need for chemotherapeutic remedies to counter the onset of taxane resistance, particularly in breast, ovarian, prostate and other cancer patients.|
• Also, there is a need to discover a priori which patients will be likely to respond to taxols.|
• As drug resistance poses a major limitation to the efficacy of taxanes, the discovery by Dr. Zetter of miRNA135a's connection to drug resistance opens up a new avenue to modulate chemotherapeutic drug response and sensitize cancer cells to drug treatment.||
• It is also possible that miRNA135a could be used as a biomarker for selecting patients likely to respond to taxane therapy. ||
Exclusive license available and/or sponsored research
Key Publications: miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo. Holleman A, Chung I, Olsen RR, Kwak B, Mizokami A, Saijo N, Parissenti A, Duan Z, Voest EE, Zetter BR. Oncogene. 2011 Oct 27;30(43):4386-98. doi: 10.1038/onc.2011.148. Epub 2011 May 9. PMID:21552288
IPStatus: Pat. Pend.