Methods of Treating Cancer and Ischemia Diseases by Inhibition and Intervention of ATR Prolyl Isomerization

Project ID: D2021-42

Background:

Cell death and immortality are closely associated with cancer and cancer therapeutics, as oncogenesis requires a compromise of apoptosis while most cancer therapies depend on apoptopsis. Precise regulation of programmed cell death (apoptosis) is essential for cellular and organ homeostasis. Hyperactive apoptosis is associated with human diseases such as myocardial infarction, ischemic stroke, and immunodeficiency. In contrast, dysfunctional apoptosis is highly relevant to oncogenesis and, also, cancer treatment. While the mechanisms regulating apoptotic pathways are extensively investigated and well defined, there is limited progress in understanding how antiapoptotic pathways protect cells. Unveiling new mechanisms involved in regulating apoptosis would be significant in disease prevention, diagnosis, and treatment. In addition, the underlying mechanisms as to how silent oncogenic mutations become active during aging remain elusive and defining the mechanisms requires a reliable aging-dependent oncogenesis model. There remains a need in the art for new and improved cancer treatments.

Invention Summary:

Researchers at the University of Toledo have developed a method for treating cancer comprising administering to a subject effective amount of inhibitor(s) to inhibit cis-ATR together with a cancer therapeutic drug to treat the cancer. The novel mechanism-driven approach lowers apoptosis resistance barriers to sensitize common types of drug resistant tumors.

 Advantages:

1. The potential treatment is expected to have minimal side-effects as compared to conventional cancer treatments.
2. The potential treatment could be particularly efficient for certain types of drug resistant cancers by targeting a specific type of collateral sensitivity.

Application:

Cancer treatment.

Publications:

1. ATR Plays a Direct Antiapoptotic Role at Mitochondria Which Is Regulated by Prolyl Isomerase Pin1 Benjamin A. Hilton,^1,# Zhengke Li,^1,# Phillip R. Musich,¹ Hui Wang,¹ Brian M. Cartwright,¹ Moises Serrano,¹ Xiao Zhen Zhou,² Kun Ping Lu,² and Yue Zou^1,*
2. Phosphorylation-Dependent Pin1 Isomerization of ATR: Its Role in Regulating ATR’s Anti-apoptotic Function at Mitochondria, and the Implications in Cancer Yetunde Makinwa,¹ Phillip R. Musich,² and Yue Zou^1,2,*

IP Status: Patent Pending