On March 27, 2024 LIXTE Biotechnology Holdings, Inc. ("LIXTE" or the "Company") (Nasdaq: LIXT and LIXTW), a clinical stage pharmaceutical company, reported publication of pre-clinical data in the online journal, Cancer Discovery, showing that its lead clinical compound, LB-100, can force cancer cells to give up their cancer-causing properties in a paper entitled "Paradoxical activation of oncogenic signaling as a cancer treatment strategy (Press release, Lixte Biotechnology, MAR 27, 2024, View Source [SID1234641569])." The finding opens a potentially new treatment strategy in addition to LIXTE’s current three clinical trials.
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As will be published in the July 2024 issue and posted online today, LB-100 was shown to trigger hyper-activation of the signals that are responsible for the deregulated proliferation of cancer cells, which is the opposite of most of the current generation of cancer therapies. The deliberate hyper-activation of cancer signals becomes lethal when combined with an inhibitor of the WEE1 kinase. This well-tolerated combination proved to be highly effective in killing colon cancer cells in animal models of cancer and in cell culture.
Resistance to therapy is the leading cause of death due to cancer. Resistance to LB-100 therapy, however, has been shown to be associated with cancer cells becoming less malignant. Specifically, colon cancer cells that developed resistance to LB-100 had lost many of the features that make the cells cancerous in the first place and were unable to form tumors in experimental animal models.
This "tumor suppressive drug resistance" stems from the unique features of LB-100. Although cancer-causing signals force cancer cells to become more cancerous, the hyper-activation of these signals by LB-100 forces cancer cells to suppress these signals and thus become less cancerous.
The team of scientists reporting these findings was headed by Professor René Bernards at the Netherlands Cancer Institute and Oncode Institute, Amsterdam. Professor Bernards is a a leader in the field of molecular carcinogenesis and is a member of the Board of Directors of LIXTE.
Bas van der Baan, Chief Executive Officer of LIXTE, said, "The effect of LB-100 on cancer cells is unique in that the only way for cancer cells to escape death is to evolve toward a less cancerous behavior. We look forward to testing this concept clinically, which is distinct from the well-characterized enhancement of checkpoint immunotherapy and chemotherapy by LB-100 currently being tested in three clinical trials."