Pre-clinical Study results show TUSC2 overexpression reduces colony formation, neurosphere formation and promotes apoptosis in vitro, and suppresses tumor growth in vivo
Study adds to the growing body of research examining TUSC2 as a target for multiple other cancers
TUSC2 is the tumor suppressor gene used in the Company's lead drug candidate, REQORSA® (quaratusugene ozeplasmid)
Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, today announced that independent researchers recently presented preclinical data on the tumor suppressor gene, TUSC2, reporting that it functions as a novel tumor suppressor for glioblastoma. TUSC2 is the tumor suppressor gene that is reexpressed in tumors using REQORSA® Therapy treatment, Genprex's lead drug candidate. Genprex has no affiliation with these researchers.
The independent researchers presented their abstract, titled, "Investigating TUSC2 for its tumor suppressive functions in glioblastoma and its role in gliomagenesis," at the 2023 American Association for Cancer Research Annual Meeting on April 17. The abstract reports TUSC2 protein expression, but not mRNA expression, to be significantly decreased in glioblastoma as compared to normal brain. TUSC2 protein is destabilized in glioblastoma due to polyubiquitination by E3 ligase, neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4), and degradation by the proteasome. The researchers determined that NEDD4 targets TUSC2 on lysine residue K71.
The researchers also reported that TUSC2 overexpression reduced colony formation and neurosphere formation and promoted apoptosis of glioblastoma cells in vitro, and suppressed tumor growth in vivo. Further, glioblastoma cells with CRISPR-mediated knockout (KO) of TUSC2 were highly aggressive in vitro and in vivo, demonstrating the role of TUSC2 as a novel tumor suppressor for glioblastoma.
In the study, researchers performed immunoprecipitation-mass spectrometry analysis to identify TUSC2-interacting proteins in both normal human astrocytes and glioblastoma cell lines. Results showed 95 and 88 TUSC2-interacting proteins in astrocytes and glioblastoma cell lines respectively, and 27 proteins were found to interact with TUSC2 in both astrocytes and glioblastoma.
"This research supports the growing body of studies evaluating TUSC2 as a target in oncology, and potentially an effective treatment, for many types of cancer," said Rodney Varner, Chairman, President and Chief Executive Officer of Genprex. "We are encouraged by the increasing number of research institutions and independent researchers producing positive data on TUSC2, which provide additional support for REQORSA® and its therapeutic potential against cancers."
REQORSA® Therapy is currently in development for the treatment of non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). REQORSA® consists of the TUSC2 gene expressing plasmid encapsulated in non-viral nanoparticles made from lipid molecules (the Company's ONCOPREX® Nanoparticle Delivery System) with a positive electrical charge. REQORSA® is injected intravenously and specifically targets cancer cells, taking advantage of leaky tumor vascularity, increased tumor pinocytosis, and attraction of positively charged lipid nanoparticles to negatively charged cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing their uptake by normal tissue.
According to the National Brain Tumor Society, glioblastoma is one of the most complex, deadly, and treatment-resistant cancers. More than 13,000 Americans were expected to receive a glioblastoma diagnosis in 2022. Glioblastoma accounts for 49.1 percent of all primary malignant brain tumors. There have only been five drugs and one device ever approved by the U.S. Food and Drug Administration for the treatment of glioblastoma.
Other independent researchers and studies have found that TUSC2 therapy may benefit other types of cancer, including head and neck, breast (including triple-negative breast cancer), renal cell (kidney), thyroid, and soft tissue sarcoma, as well as NSCLC and SCLC. For more information and additional studies supporting TUSC2, please refer to our Bibliography Page.
About Genprex, Inc.
Genprex, Inc. is a
clinical-stage gene therapy company focused on developing life-changing
therapies for patients with cancer and diabetes. Genprex's technologies
are designed to administer disease-fighting genes to provide new
therapies for large patient populations with cancer and diabetes who
currently have limited treatment options. Genprex works with world-class
institutions and collaborators to develop drug candidates to further
its pipeline of gene therapies in order to provide novel treatment
approaches. Genprex's oncology program utilizes its proprietary,
non-viral ONCOPREX® Nanoparticle Delivery System which encapsulates the
gene-expressing plasmids using lipid nanoparticles. The resultant
product is administered intravenously, where it is taken up by tumor
cells that then express tumor suppressor proteins that were deficient in
the tumor. The Company's lead product candidate, REQORSA®
(quaratusugene ozeplasmid), is being evaluated in three clinical trials
as a treatment for non-small cell lung cancer (NSCLC) and small cell
lung cancer (SCLC). Both NSCLC clinical programs received a Fast Track
Designation from the Food and Drug Administration. Genprex's diabetes
gene therapy approach is comprised of a novel infusion process that uses
an adeno-associated virus (AAV) vector to deliver Pdx1 and MafA genes
directly to the pancreas. In models of Type 1 diabetes, GPX-002
transforms alpha cells in the pancreas into functional beta-like cells,
which can produce insulin but are distinct enough from beta cells to
evade the body's immune system. In a similar approach, GPX-003 for Type 2
diabetes, where autoimmunity is not at play, is believed to rejuvenate
and replenish exhausted beta cells.
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