HOUSTON--(BUSINESS WIRE)--A study conducted at The Wistar Institute in collaboration with The University of Texas Southwestern Medical Center has demonstrated the efficacy of targeting aberrantly active telomerase to treat therapy-resistant melanoma. The research was published in the journal Clinical Cancer Research (http://clincancerres.aacrjournals.org/content/early/2018/03/21/1078-0432.CCR-17-2773).
A hallmark of several cancer types, including melanoma, is increased telomerase activation. Telomerase is an enzyme responsible for elongating telomeres which protect the integrity of chromosome ends during cell replication. While absent in most normal cells, telomerase is highly active in cancer cells, driving continuous cell divisions.
“Telomerase is an almost universal oncology target. In the present study, we provide a scientific rationale for the development of new clinical cancer treatments based on targeting telomeres in cancer cells,” said Jerry W. Shay, co-author of the study, and professor of Cell Biology at UT Southwestern Medical Center.
Meenhard Herlyn, D.V.M., D.Sc., Caspar Wistar Professor in Melanoma Research and director of The Wistar Institute Melanoma Research Center, and his collaborators used a modified telomerase substrate they had previously described, 6-thio-2’-deoxyguanosine or 6-thio-dG (THIO), to utilize telomerase to induce telomere dysfunction. They demonstrated that THIO induced cell death in melanoma cells harboring BRAF gene mutations and impaired tumor growth in several BRAF-mutant mouse melanoma models without affecting the viability of normal skin cells.
The team also studied the ability of THIO treatment to stop proliferation and tumor growth of therapy-resistant melanoma cells. They created a large panel of human melanoma cell lines with acquired resistance to targeted therapy and immunotherapy and showed a general sensitivity of these cells to THIO both in vitro and in vivo.
“These exciting results add to a substantial amount of scientific data on THIO supporting our development program,” said Frank Perabo, CEO of Barricade Therapeutics. “The data suggest that THIO could be studied in future clinical trials in a first- and second-line therapy setting, or in combination with other agents to overcome intrinsic resistance.”
This work was supported by grants from NIH, DoD, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Melanoma Research Foundation.
THIO (6-thio-2′-deoxyguanosine or 6-thio-dG) specifically targets and induces damage to telomeric DNA, resulting in the selective death of tumor cells. Telomerase is an almost universal driver of tumor growth. THIO utilizes a novel mechanism of action, and in contrast to other telomerase inhibitor–based approaches, THIO is not a direct telomerase inhibitor. THIO causes telomere uncapping, leading to cancer cell death. Barricade Therapeutics is developing THIO for multiple oncology indications and has licensed the global exclusive rights from UT Southwestern, Dallas, TX.
About Barricade Therapeutics:
Barricade Therapeutics, Corp. (www.barricadetherapeutics.com) is a privately-held Biotech company based in Houston, TX. Barricade was founded based on discovery and advancement of novel first-in-class anti-cancer small molecules. The current status of the development programs is preclinical.