Highly Selective, First-in-Class CDK4 Inhibitor Promising in Ovarian Cancer

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Mice treated with 2-94 had few or no signs of lymphopenia or neutropenia, common adverse events associated with palbociclib.
Mice treated with 2-94 had few or no signs of lymphopenia or neutropenia, common adverse events associated with palbociclib.
The following article features coverage from the American Association for Cancer Research (AACR) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

2-94, a novel CDK4 inhibitor, may be a highly selective and effective treatment for ovarian cancer, according to a study being presented at the 2018 American Association for Cancer Research Annual Meeting in Chicago, Illinois.1

Ovarian cancer is characterized by overexpression of CDK4/6 and/or cyclin D1; patients with Rb-positive tumors and a low expression of p16INK4a tend to have the worst outcomes in this population. These patients are, however, likely to benefit from CDK4/6 inhibition. For this study, researchers assessed the efficacy of 2-94 against ovarian cancer in a preclinical model.

Analysis showed that 2-94 targets CDK4-cyclin D1, inhibiting the proliferation of Rb-proficient ovarian cells. 2-94 also reduced Rb phosphorylation, which led to cell cycle arrest in the G1 phase, increased apoptotic activity, and displayed a potentially synergistic relationship with mTOR, MEK, PI3K, and PARP inhibitors. 

Mice treated with oral 2-94 had slowed tumor growth and a significant improvement in survival. An analysis of the T/C ratio — the ratio of tumor volume in control vs treated mice, a common measure of efficacy — revealed that 2-94 was more effective than palbociclib, with a T/C ratio of 22% vs 31%, respectively.

Mice treated with 2-94 had few or no signs of lymphopenia or neutropenia, common adverse events associated with palbociclib.

The authors concluded that “the favourable oral pharmacokinetics, robust antitumor efficacy and excellent safety profiles make 2-94 a highly attractive candidate for development towards the clinic.”

Read more of Cancer Therapy Advisor's coverage of the American Association for Cancer Research (AACR) 2018 meeting by visiting the conference page.

Reference

  1. Mekonnen LB, Zeleke S, Lenjisa J, et al. A first-in-class CDK4 inhibitor shows excellent in vitro and in vivo efficacy against ovarian cancer. Oral presentation at: 2018 American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago, IL.

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