PracticeUpdate Oncology May 2019

CONFERENCE COVERAGE 22

The Radiation Oncology Summit:

ACRO 2019 7–9 MARCH 2019 • ORLANDO, FLORIDA, USA By the PracticeUpdate Editorial Team

Drug Targeting p53 Sensitizes Cancer Cells to Radiotherapy in Head and Neck Cancer New compound targets the most common mutation in human cancer. A PR-246, a drug that targets p53, the most common mutation in human cancers, displays antiprolif- for compounds from a National Cancer Institute database, looking for compounds that would reactivate a mutant species of the p53 tumor suppressor gene.”

doing so, it reactivates the mutant p53 gene and restores its tumor suppressive function. APR-246 is in phase II trials for myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) post-transplant maintenance and in phase III trials for MDS. A recent mechanistic study revealed that APR-246 reactivates mutant p53 by targeting cysteines 124 and 277, opening up research possibilities for rational design of novel mutant p53-targeting compounds. In this study, Dr. Nikolaev and colleagues conducted cell proliferation and radio-sen- sitization assays comparing the activity of two types of mutant HNCC lines with wild type and null HNCC lines in the presence of APR-246.

erative effects on human papilloma virus (HPV)-negative head and neck cancer cell (HNCC) lines correlating with mutant p53 status. Also, the drug displays additive effects when combined with radiation in p53-mutant HNCC lines. “There are an estimated 10 million cancer patients with p53 mutations worldwide,” presenter Anatoly Nikolaev, MD, PhD, of the University of Alabama at Birmingham told Elsevier’s PracticeUpdate . “APR-246 is a drug that was discovered and devel- oped by the Karolinska Institute in Sweden approximately 10 years ago. They screened

“More than 50% of human cancers have mutations of p53,” he continued. “Mutations of the gene result in progression of tumori- genesis and poor response to conventional treatments such as chemotherapy and radiation. It is an essential gene in tumori- genesis and has been called the guardian of the human genome because it prevents tumorigenesis,” he said. An active metabolite of APR-246 – methylene quinuclidinone – targets various proteins in the p53 complex by binding to “hotspot” mutant protein structures. By

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