Implications of Experimental Cancer Drug For Neuroblastoma

Scientists have identified the primary target of the experimental cancer drug CX-5164 for high-risk neuroblastoma patients (to improve survival), thus, revealing a possible risk for late effects of treatment as per a study at the St. Jude Children’s Research Hospital, published in the journal Nature Communications. Neuroblastoma arises from cells of the developing peripheral nervous system and is diagnosed in about 800 children annually in the U.S.

CX-5461 is a small molecule that has been widely described as a first-in-human inhibitor of the enzyme RNA polymerase 1 and is studied for more than a decade. The Phase II clinical trials of CX-5461 are underway in adults with leukemia, lymphoma, and breast cancer.

CX-5461 and Safety Concern

However, the study team found that the drug killed neuroblastoma tumor cells primarily by targeting and disrupting the activity of the different enzyme – topoisomerase II beta (TOP2β) rather than inhibiting RNA polymerase 1.

“Decades of study of an existing class of chemotherapy agents have shown that off-target drug interactions with TOP2β leave patients at risk for serious and life-threatening side effects such as acute myeloid leukemia or cardiotoxicity that emerge years later. The findings highlight a previously unappreciated safety concern with CX-5461,” says Paul Geeleher, Ph.D., St. Jude Department of Computational Biology. Thus, the study team identified safety concerns with this experimental drug that have implications for current clinical trials in adults.

“Patients enrolled in on-going CX-5461 phase II trials should be closely monitored for these late-emerging TOP2β-related adverse events,” noted the researchers.

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Source-Medindia