Vladimir Kolenko Receives Grant from the Department of Defense to Study PARP-1 inhibitors in Renal Cell Carcinoma

"Our studies have led to the identification of a novel class of histone-dependent small-molecule PARP-1 inhibitors targeting both DNA repair and transcriptional functions of PARP-1,” said Kolenko.
"Our studies have led to the identification of a novel class of histone-dependent small-molecule PARP-1 inhibitors targeting both DNA repair and transcriptional functions of PARP-1,” said Kolenko.

PHILADELPHIA (October 29, 2018) – Vladimir Kolenko, MD, PhD, an associate research professor at Fox Chase Cancer Center, has received a grant from the Department of Defense to study histone-dependent PARP-1 inhibitors in the treatment of renal cell carcinoma.

The objective of the proposal is to validate the therapeutic potential of novel PARP (poly ADP ribose polymerase)-1 inhibitors using clinically relevant cell and animal models of human clear cell renal cell carcinoma and investigate the mechanisms underlying their anti-tumor activity.

“Recent advances in cancer biology and drug discovery have provided the foundation for the development of targeted agents. While PARP-1 plays a key role in repairing DNA damage in tumor cells, it also serves as a potent transcriptional modulator of various tumor-promoting genes. Our studies have led to the identification of a novel class of histone-dependent small-molecule PARP-1 inhibitors targeting both DNA repair and transcriptional functions of PARP-1,” said Kolenko.

Kolenko and colleagues will evaluate the laboratory-based anti-tumor activity of histone-dependent PARP-1 inhibitors; examine the absorption, distribution, metabolism, excretion and pharmacodynamics properties of histone-dependent PARP-1 inhibitors; and determine the efficacy of histone-dependent PARP-1 inhibitors using patient derived xenograft models of human clear cell renal cell carcinoma.

The grant awards $566,149 for a period of three years, beginning in September 2018 and ending in August 2021.

This work was supported by the Congressionally Directed Medical Research Programs through the Kidney Cancer Research Program under Award No W81XWH1810449. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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