Outside research shows that in models of colorectal, triple-negative breast and pancreatic cancer, LB-100 induces molecular changes that render the cancers more vulnerable to immunotherapy
PASADENA, CA, Jan. 05, 2022 (GLOBE NEWSWIRE) -- Lixte Biotechnology Holdings, Inc. (Nasdaq: LIXT), a clinical-stage drug discovery company developing pharmacologically active drugs for use in cancer treatment, announced today that in preclinical studies its lead clinical compound, LB-100, a protein phosphatase (PP2A) inhibitor, was found to increase the responsiveness of diverse cancers to immunotherapy. In Nature Communications (15 Dec 2021), lead author Yu-Ting Yen and colleagues at the China Medical University and Hospital, Taichung, Taiwan reported that treatment with LB-100 is associated with new antigen production, tumor infiltration of cytotoxic T cells, and enhanced responsiveness to immune checkpoint blockade in mouse models of colorectal, triple-negative breast, and pancreatic cancer. The authors state that “these data indicate that PP2A inhibition can be used to change the intrinsic and extrinsic factors of tumors to improve the success rate of anti-cancer immunotherapy.”
Lixte’s founder and CEO, John S. Kovach M.D, commented that “recent advances in therapy with immune checkpoint inhibitors have been a true breakthrough in the development of more effective and less toxic treatment for many cancers. Unfortunately, most cancer patients do not respond to immunotherapy. There are widespread efforts to find pharmacologic and/or immunologic ways to turn unresponsive (‘cold’) tumors into responsive (‘hot’) tumors. Cancers with a molecular abnormality termed microsatellite-instability (MSI) stemming from a defect in a DNA repair enzyme are generally ‘hot’ tumors, that is, tumors responsive to immunotherapy. Yen and colleagues now report that pharmacologic inhibition of PP2A by LB-100 modifies two distinct molecular pathways resulting in conversion of microsatellite stable (MSS) tumors into MSI tumors sensitive immune checkpoint blockade therapy.”
Dr. Kovach concluded: “The results of Yen et al. raise the possibility that the addition of LB-100 to immunotherapy may be a simple way to convert ‘cold’ into ‘hot’ tumors, thereby increasing the percentage of patients responsive to immunotherapy. Lixte recently initiated a clinical trial in patients with previously untreated extensive stage small cell lung cancer in which LB-100 is first added to chemotherapy and an immune checkpoint blocker and then administered with the immune blocker alone in the maintenance phase of treatment (NCT04560972). Lixte is interested in collaborative studies designed to determine whether LB-100 broadly enhances the benefit of immunotherapy. Immune checkpoint blockers are now approved for treatment of at least 20 cancer types.”
About Lixte Biotechnology Holdings, Inc.
Lixte Biotechnology Holdings, Inc. (Nasdaq: LIXT) is a clinical-stage pharmaceutical company dedicated to discovering drugs for more effective treatments for many forms of cancer and other serious common diseases. A major driver of cancer is defects in the switches that turn the biochemical pathways in cells on and off. Most cancer research over the past 30 years has focused on the “on” switches because the “off” switches, especially the master “off” switch protein phosphatase (PP2A), were believed to cause intolerable toxicity in patients. Lixte has achieved a breakthrough with its novel, first-in-class lead clinical compound and PP2A inhibitor, LB-100, by demonstrating that this compound is readily tolerated in cancer patients at doses associated with anti-cancer activity. This innovative approach encourages cancer cells damaged by chemo or other cancer therapies to continue to replicate before repairing the damage, leading to more efficient killing of those cells. LB-100 is being tested in three clinical cancer treatment studies with others in planning. www.lixte.com
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