Genprex to present results preclinical data from Reqorsa study

Genprex (GNPX) announced that its research collaborators will present at the upcoming 2025 American Association for Cancer Research, or AACR, Annual Meeting being held April 25-30, in Chicago, Illinois. The collaborators will present positive preclinical data from a study of its lead drug candidate, Reqorsa Gene Therapy, or quaratusugene ozeplasmid, for the treatment of KRASG12C mutant non-small cell lung cancer, or NSCLC. Acquired resistance, or AR, to Lumakras, or sotorasib, the first FDA-approved KRASi, poses a significant challenge in the treatment of KRASG12C mutant NSCLC. Despite initial responses, patients invariably develop resistance, necessitating alternative therapeutic strategies. The mechanisms underlying AR include the emergence of additional mutations in the KRAS gene, reactivation of the KRAS pathway, or activation of alternative signaling pathways. TUSC2, a potent tumor suppressor gene with immunogenic properties, exhibits multifunctional activity by inhibiting downstream signaling pathways, including MAPK and mTOR; arresting the growth and proliferation of cancer cells; inducing tumor cell death; and activating innate and adaptive immune responses. In this study, researchers demonstrated that TUSC2 gene therapy, or REQORSA, effectively overcomes sotorasib AR in KRASG12C mutant NSCLC mouse xenografts. The data indicate that TUSC2 transfection significantly reduced colony formation in two AR cell lines. Transfection of TUSC2 also markedly increased apoptosis in AR cells. Re-expression of TUSC2 into AR PDXOs significantly decreased the viability of organoids compared with the empty vector. The H23AR tumors exhibited significantly lower sensitivity to sotorasib than their parental counterparts. In conclusion, researchers demonstrated that REQORSA, alone or in combination with sotorasib, induced apoptosis, inhibited colony formation, and showed significant antitumor efficacy in KRASG12C mutant sotorasib-acquired resistant xenograft and PDX tumors.