AIDS Drug May Restrict Proliferation of Cancer Cells

The clinically approved AIDS drug ABC (Abacavir) can reduce proliferation and induce differentiation of human medulloblastoma cells through the downregulation of telomerase activity, which may make it an effective therapeutic strategy for the treatment of the highly malignant primary brain tumors, according to research published in the International Journal of Cancer.

“We found that ABC not only downregulates telomerase activity but also reduces proliferation and induces differentiation, suggesting that its use could be an effective therapeutic strategy for the treatment of telomerase expressing tumors, such as medulloblastomas,” says lead researcher Francesca Pentimalli, PhD, an assistant adjunct professor at the Sbarro Institute for Cancer Research and Molecular Medicine, at the Center for Biotechnology in the College of Science & Technology at Temple University in Philadelphia, PA, and a researcher at CROM, the Center of Oncology Research, in Mercogliano, Avellino, Italy.

The lead authors of the paper were Alessandra Rossi, PhD, a Research Fellow at the Sbarro Institute and Antonio Giordano, MD, PhD, the Founder and President of the Sbarro Health Research Organization, the Director of the Sbarro Institute and the President of the Scientific Advisory Board of CROM.

The study was conducted by a collaboration of researchers from the Sbarro Institute, CROM, the University of Siena, Siena, Italy; the Department of Computer and Information Sciences (DISI), University of Genoa, Genoa, Italy; the Department of Pharmacology, University of Salerno, Fisciano, Salerno, Italy; and the Division of Medical Oncology B, Regina Elena Cancer Institute, Rome, Italy.

ABC is one of the most efficacious nucleoside analogues, with a well-characterized inhibitory activity on reverse transcriptase enzymes of retroviral origin. Recently, it has been shown to also inhibit human telomerase activity.

Telomerase activity seems to be required in essentially all tumors for the immortalization of a subset of cells, including cancer stem cells. In fact, many cancer cells are dependent on telomerase for their continued proliferation.

Researchers tested whether ABC could inhibit telomerase in medulloblastoma, the most common malignant tumor of the central nervous system in children. Despite improvements in the overall survival rate owing to the multimodality of treatment, medulloblastoma remains a deadly disease.

Dr. Pentimalli suggests that one advantage of ABC, when compared with other tested compounds targeting telomerase that are currently in preclinical studies, is that ABC has been used to treat AIDS for many years, which “would have obvious advantages given its favorable safety profile and its epidemiological record of generally good tolerance to long-term administration.”

Moreover, she notes, as the blood-brain barrier restricts the entry of hydrophilic and large lipophilic compounds into the brain, the lipophilic nature of ABC, which enables it to pass through the blood brain barrier more easily, represents yet another advantage for its possible use for the treatment of medulloblastoma.

“Our report suggests further consideration and study of the use of ABC as an anti-telomerase agent in cancer.”

Sbarro Health Research Organization (http://www.shro.org), a nonprofit charitable organization, is a leader in cancer, cardiovascular, and diabetes research, and supports the Sbarro Institute for Cancer Research and Molecular Medicine located at the Center for Biotechnology in the College of Science & Technology at Temple University in Philadelphia, PA.

Source: Sbarro Health Research Organization (SHRO)