Abstract
Chemotherapies targeting deoxynucleotide triphosphate synthesis are of high medical interest in the treatment of gynecologic malignancies. In this article, we focus on targeted inhibitors of ribonucleotide reductase, an enzyme in charge of ribonucleotide reduction to their corresponding deoxyribonucleotide to be used as the building blocks of DNA. We also discuss human clinical trials have utilized ribonucleotide reductase subunit-specific inhibitors, particularly trials for women with cervical cancer.
Highlights
A unifying treatment stratagem for women with advanced staged gynecologic malignancies remains elusive
The American Cancer Society estimates 88,080 American women will be newly diagnosed with a gynecologic malignancy in 2011, with 29,590 (34%) fatalities attributed to gynecologic malignant disease progression [1]
We discuss current concepts of disrupted regulation of ribonucleotide reductase (RR) and tested treatments aimed at therapeutically modifying RR-mediated dNTP supply needed for repair of DNA damage in human gynecologic cancers
Summary
A unifying treatment stratagem for women with advanced staged gynecologic malignancies remains elusive. Gynecologic cancers pose a great health concern among women worldwide, with as many as 1.1 million newly diagnosed gynecologic cancers recorded by international cancer registries [2]. Of these new cases, cervical cancer will develop in an estimated 530,000 women this year worldwide [2]. We discuss current concepts of disrupted regulation of ribonucleotide reductase (RR) and tested treatments aimed at therapeutically modifying RR-mediated dNTP supply needed for repair of DNA damage in human gynecologic cancers. Much of this work has been the result of human translational and scientific studies conducted in cervical cancer clinical trials
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