New Preclinical Data for THIO in BRAF-Mutant Mouse Melanoma Models
25 März 2018 - 1:34AM
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.
About THIO:
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.
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Barricade Therapeutics, Corp.Vlad Vitoc, MD MBA,
713-963-3670vvitoc@barricadetherapeutics.com