Novel Approach to Enhance CDK4/6 Inhibitor Therapy

Name: Novel Approach to Enhance CDK4/6 Inhibitor Therapy
Brand: University of Pittsburgh
SKU: 07517

A University of Pittsburgh researcher has identified long non-coding RNAs (lncRNAs) that modulate response to cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy. Using small interfering RNA (siRNA) or antisense oligonucleotides (ASOs), it is possible to selectively control expression of these oncogenic lncRNAs, improving the response to CDK4/6i therapy. Additionally, detection of these lncRNAs could act as biomarkers to develop personalized treatment strategies, improving outcomes in difficult to treat patients.

Description

Research has uncovered the role of some lncRNAs in cancer, including functions in tumorigenesis, metastasis, and response to cancer treatment. Some lncRNAs can promote resistance to treatment and limit treatment efficacy, while others can enhance sensitivity to treatment. Modulating the expression of these lncRNAs could be a novel target in cancer therapy. Recently, three lncRNAs have been discovered to regulate cancer proliferation and modulate palbociclib CDK4/6i therapy in breast cancer cells. With this knowledge, siRNAs have been developed to inhibit these oncogenic lncRNAs which could be a novel treatment or used to enhance existing CDK4/6i therapy.

Applications

- Breast cancers
- Lung cancers
- Gastric cancers

Advantages

CDK4/6 inhibitors are a class of treatments used to target estrogen receptor positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers. CDK4/6 inhibitors suppress breast cancer cell proliferation blocking cell cycle progression. However, patient response is not uniform and the development of a biomarker to identify patients most likely to benefit from CDK4/6i therapy could improve decision-making around treatment options for cancer patients.

This novel approach could result in downregulation of oncogenic lncRNAs using ASOs or siRNA to interfere with cell proliferation processes and improve the efficacy of the CDK4/6i. Additionally, screening the cancer transcriptome for the presence of key lncRNAs could identify patients best suited to individualized therapies.

Invention Readiness

Three lncRNAs have been discovered to promote cancer cell proliferation and modulate CDK4/6i response in cells. In animal models, upregulation of these lncRNAs drove tumor growth whereas downregulation using siRNA increased rates of cell survival in vitro. Further work is required, but this novel approach for targeting and regulating oncogenic lncRNAs could also treat cancers including gastric and bladder cancer, lymphoma, and neuroblastoma.

IP Status

Patent Pending

Related Publication(s)

Wang, Y., Zhao, Y., Hu, J., Wang, Z., Pattarayan, D., Li, S., Zhang, Y., Wang, X., Wang, Y., Xie, W., Zhang, M., & Yang, D. (2026). CRISPR activation screens identify oncogenic lncRNAs that are susceptible to CDK4/6 inhibitor treatment. Nature Communications. https://doi.org/10.1038/s41467-026-70816-2

Li, S., Wang, Z., Nguyen, P., Wang, Y., Zhao, Y., Wang, Y., Chen, Y., Huang, H., Wang, X., Zhang, Y., Huang, Y., Pattarayan, D., Zhang, M., Liu, Y., Li, S., & Yang, D. (2026). MYC-bound enhancer RNAs in cis regulate gene transcription and tumorigenesis. Science Advances, 12(17). https://doi.org/10.1126/sciadv.aeb5147

Related Technology