Independent Researchers Find That TUSC2, the Gene Delivered by Genprex's REQORSA®, Functions as a Novel Tumor Suppressor for Glioblastoma
Genprex, Inc. (NASDAQ: GNPX) announced pre-clinical findings revealing that the tumor suppressor gene TUSC2 significantly inhibits glioblastoma. Independent researchers presented these results at the 2023 American Association for Cancer Research Annual Meeting. The study showed that TUSC2 overexpression decreases colony and neurosphere formation, induces apoptosis in glioblastoma cells in vitro, and suppresses tumor growth in vivo. Additionally, the research found that TUSC2 protein levels were significantly lower in glioblastoma compared to normal brain tissue. The study supports ongoing investigations into TUSC2 as a potential target for various cancers, enhancing the therapeutic potential of Genprex's lead drug candidate, REQORSA®, which is currently being evaluated for non-small cell lung cancer and small cell lung cancer.
- Preclinical study indicates TUSC2 may be an effective tumor suppressor for glioblastoma.
- REQORSA® demonstrated efficacy in reducing tumor growth and promoting apoptosis in glioblastoma cells.
- Ongoing studies suggest TUSC2's potential application in treating multiple cancer types.
- None.
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)
AUSTIN, Texas, April 18, 2023 /PRNewswire/ -- 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.
For more information, please visit the Company's web site at www.genprex.com or follow Genprex on Twitter, Facebook and LinkedIn.
Cautionary Language Concerning Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are made on the basis of the current beliefs, expectations and assumptions of management, are not guarantees of performance and are subject to significant risks and uncertainty. These forward-looking statements should, therefore, be considered in light of various important factors, including those set forth in Genprex's reports that it files from time to time with the Securities and Exchange Commission and which you should review, including those statements under "Item 1A – Risk Factors" in Genprex's Annual Report on Form 10-K for the year ended December 31, 2022.
Because forward-looking statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Genprex's ability to advance the clinical development, manufacturing and commercialization of its product candidates in accordance with projected timelines; the timing and success of Genprex's clinical trials and regulatory approvals; the effect of Genprex's product candidates, alone and in combination with other therapies, on cancer and diabetes; Genprex's future growth and financial status, including Genprex's ability to continue to obtain capital to meet its long-term liquidity needs on acceptable terms, or at all; Genprex's commercial and strategic partnerships, including those with its third party vendors, suppliers and manufacturers and their ability to successfully perform and scale up the manufacture of its product candidates; and Genprex's intellectual property and licenses.
These forward-looking statements should not be relied upon as predictions of future events and Genprex cannot assure you that the events or circumstances discussed or reflected in these statements will be achieved or will occur. If such forward-looking statements prove to be inaccurate, the inaccuracy may be material. You should not regard these statements as a representation or warranty by Genprex or any other person that Genprex will achieve its objectives and plans in any specified timeframe, or at all. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Genprex disclaims any obligation to publicly update or release any revisions to these forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release or to reflect the occurrence of unanticipated events, except as required by law.
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