LA JOLLA, Calif., March 11, 2019 (GLOBE NEWSWIRE) -- ActivX Biosciences, Inc., a wholly-owned subsidiary of Kyorin Pharmaceutical Co., Ltd. (Tokyo), announces a report published in a high profile, peer-reviewed journal, Molecular Cancer Therapeutics, (http://mct.aacrjournals.org/content/early/recent?utm_source=early&utm_medium=dropdown&utm_campaign=menu) proposing the molecular mechanism determining the sensitivity or resistance to treatment with CDK4/6 inhibitors.
The CDK4/6 inhibitors palbociclib (Ibrance®, Pfizer), ribociclib (Kisqali®, Novartis) and abemaciclib (Verzenio®, Lilly) are approved for the treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. While these drugs have demonstrated clinical efficacy, there remains a need for biomarkers to predict patient response as well as to extend the use of these drugs beyond ER-positive breast cancer. Scientists at ActivX Biosciences, and their collaborators at Vall d’Hebron Institute of Oncology (VHIO), Barcelona, showed that high levels of p16/CDKN2A, an endogenous regulator of CDK4/6, could serve as a biomarker to identify patients unlikely to respond to CDK4/6 inhibitors, thus sparing them from unnecessary treatment.
Using the KiNativ® platform, the authors assessed CDK4/6 target engagement in a panel of cell lines with known alterations in p16-CDK4 binding and showed that the interaction between p16 and CDK4 limits target engagement by CDK4/6 inhibitor drugs. Further research demonstrated that high levels of p16 were correlated with a lack of biological response in a diverse panel of cell lines that included the highly aggressive triple-negative breast cancer subtype.
“We believe our findings will help define patient selection criteria for future clinical trials and extend the therapeutic benefits of these important drugs to patients with other types of cancer,” commented Jennifer Green, lead author of the study. "Identifying mechanisms for cell type-specific target engagement showcases the power of our technology. I’m excited to see what other examples are uncovered as the method is more broadly utilized.”
The KiNativ platform, operated by ActivX, provides an unrivaled ability to quantitatively profile kinase inhibitors against native kinases in virtually any cell or tissue lysate. It is currently utilized by over 90 pharmaceutical/biotech companies and academic institutions. To learn more about KiNativ and its applications, go to www.kinativ.com or call ActivX Biosciences at 858 526-2515.
About ActivX Biosciences, Inc.
ActivX Biosciences, Inc. (www.activx.com) located in La Jolla, California, is a wholly-owned subsidiary of Tokyo-based Kyorin Pharmaceutical Co. Ltd, and has drug discovery and proteomics technology capabilities. The company applies proprietary chemical technologies and high-throughput protein analysis to the drug discovery and development process. By focusing on functional proteins, ActivX® addresses disease mechanisms directly, in contrast to approaches such as expression profiling, in which the measured analyte is several steps removed from the site of drug action. ActivX® and its partners are using ActivX's proprietary technology to address critical challenges in drug discovery, including selectivity profiling of candidate drug molecules across whole protein families in biological samples to guide their medicinal chemistry efforts, identifying novel drug targets and biomarkers, and characterizing off-target activities of candidate and established drugs to understand the basis of their efficacy and/or toxicity.