ActivX Biosciences reports key findings that could impact the use of clinically approved CDK4/6 inhibitors in the treatment of cancer patients

March 11, 2019

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, 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 or call ActivX Biosciences at 858 526-2515.

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