NEWTOWN, PA — Onconova Therapeutics, Inc. (NASDAQ: ONTX) has unveiled preclinical data that demonstrates the superior performance of narazaciclib, a multi-kinase inhibitor, over palbociclib and other CDK4/6 inhibitors. The data presented in a poster at the San Antonio Breast Cancer Symposium (SABCS) on December 8, 2023, highlighted narazaciclib’s broad anti-tumor activity and increased anti-tumor immunity.
The objective of the research was to compare the activity of narazaciclib and its metabolite, ON1232580, with FDA-approved CDK4/6 inhibitor palbociclib. The study employed panels of resistant, mutated, or modified tumor cell lines to evaluate each agent’s activity and potency to inhibit growth and reduce cell line viability.
The results showed that while narazaciclib and palbociclib affect a similar set of cell pathway targets, including Rb, Akt, and mTOR, narazaciclib impacts more kinases than palbociclib. This expanded scope could improve narazaciclib’s efficacy by overcoming cancer resistance pathways not targeted by other CDK4/6 inhibitors.
A deeper analysis in human breast and ovarian cells/cell lines revealed that high BUB1 kinase expression is associated with low survival in patients with breast and uterine corpus endometrial carcinomas (UCEC). Narazaciclib showed potential for use in breast cancer and UCEC, either as monotherapy or in combination with other agents, due to its ability to degrade BUB1 kinase.
Furthermore, narazaciclib demonstrated a potent ability to inhibit cell viability in a wide range of breast and ovarian cancer cell panels. It also produced significantly higher increases in T-cell recruiting chemokines, suggesting its potential to promote greater levels of anti-tumor immunity and enhance efficacy.
In conclusion, the expansive analysis of narazaciclib shows that it has the potential to differentiate itself with its multi-kinase profile, potent ability to inhibit cell viability, and ability to produce significantly higher increases in T-cell recruiting chemokines. These findings support the potential use of narazaciclib in patients with breast and ovarian cancer, as well as its potential in LGEEC, based on broad, differentiated multi-kinase activity, supported by potential anti-tumor activity and anti-tumor immunity, compared to palbociclib and other CDK4/6 inhibitors.
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