Due to a system-wide technology update, we are experiencing extremely high call volume. We appreciate your patience with our operators during this time. Thank you for choosing Fox Chase Cancer Center.


Important Public Notice: ANCC Magnet Recognition Program® - Site Visit through November 4, 2022. Click here to learn more.


MicroRNAs Targeting CDK4 /6 -Cell Cycle Pathway as Treatment for Cancer

Reference No. 424-WE


Uncontrolled cellular proliferation is a hallmark of cancer. Dysregulation of the cell-cycle machinery and activation of cyclin-dependent kinases (CDKs) to promote cell-cycle progression is a key mechanism in many cancer pathologies. The first-generation of nonselective CDK inhibitors, designed to inhibit this proliferation, showed high degree of toxicity and lacked efficacy. In contrast, a new generation of selective CDK4/6 inhibitors, including small molecules such as ribociclib, abemaciclib and palbociclib,has enabled tumor types in which CDK4/6 has a pivotal role be targeted with improved effectiveness, and fewer adverse side effects. However, CDK4/6 inhibitors are limited in their single-agent efficacy and there is emerging evidence acquired resistance for these small molecules. Recent research also suggests that long-term treatment with CDK4/6 inhibitors can hinder the antitumor immune response by causing senescence in normal cells. Thus, there is need to develop a new class of selective CDK4/6 inhibitors.

Summary of Invention

Dr. Wafik El-Deiry and his team at the Fox Chase Cancer Center have identified four unique microRNAs (miRNAs) that inhibit the activity of CDK4/6. Unlike the small molecule approach where they target CDK4/6 directly, these miRNAs function by silencing the mRNA for production of CDK4/6 thereby reducing the protein levels of CDK 4/6 in cancer cells. The miRNAs display significant anti-proliferative effects in colorectal cancer, pancreatic cancer and melanoma cell lines. In addition, the miRNAs also engage the apoptosis pathway by down-regulating anti-apoptotic markers such as XIAP, BClxL and FOXM1. Synergies between these miRNAs and drugs currently used in treatment of colorectal cancer such as irinotecan and 5-fluorouracil have been observed.

Reference: Lulla A.R. et al., “miR-6883 Family miRNAs Target CDK4/6 to Induce G1 Phase Cell-Cycle Arrest in Colon Cancer Cells” 2017, Cancer Res. Dec 15; 77 (24): 6902-6913. https://www.ncbi.nlm.nih.gov/pubmed/29061672


  • Broad-range and yet specific targeting of multiple oncogenes in cell cycle and apoptosis pathways
  • New line of therapeutics, and/or an alternate adjuvant therapy for cancers that dependent on the activity of CDK4/6 such as colorectal, breast, lung cancers, melanoma and leukemia

Patent Status: Patent application filed

For licensing/partnering information, please contact:
Inna Khartchenko, MS, MBA
Director, Technology Transfer
Tel.: 215-214-3989
E-mail: inna.khartchenko@fccc.edu

Connect with Fox Chase