(ChemotherapyAdvisor) – A Phase 1 preclinical trial has demonstrated a synergistic antitumor activity of AKT inhibitor MK2206 and FUS1-nanoparticles in LKB1 mutant NSCLC. The study was presented at the Annual Meeting of the American Association for Cancer Research (AACR) (Abstract No. 870).
In this study, researchers aimed to compare the efficacy of Oncoprex (a FUS1-mediated nanoparticle-based therapy) combined with Merck’s MK2206 to that of Oncoprex or MK2206 monotherapy in animal models bearing H322 LKB1-mutant human lung cancer tumors.
“FUS1, a novel tumor suppressor gene in the human chromosome, is deleted in many cancers. Previous studies showed that FUS1 regulates the activation of multiple oncogenic kinases,” the authors wrote. “MK2206 is a highly selective non-ATP-competitive allosteric inhibitor of AKT currently being evaluated in early-phase clinical trials for treatment of patients with lung cancer.” In addition, LKB1 is a kinase inactivated in 30% of lung cancers.
In this preclinical study, combination therapy resulted in a 2.5-fold reduction in tumor volume over MK2206 alone. The studies revealed that Oncoprex therapy sensitized the response of NSCLC cells to MK2206, resulting in a marked increase in growth suppression and apoptosis in LKB1-mutant NSCLC.
The authors concluded: “Results from the study show that Oncoprex may play a role in modulating the sensitivity of lung cancer cells to AKT inhibition, and suggest that a combination of Oncoprex and MK2206 may be an effective treatment strategy for LKB1 mutant human lung cancers.”
Previous studies revealed the antitumor activity of intravenous Oncoprex monotherapy in lung cancer patients, while other previously published animal studies demonstrated the synergistic antitumor activity when Oncoprex is combined with a variety of kinase inhibitory agents including erlotinib and gefitinib. Moreover, a Phase 1/2 clinical trial evaluating Oncoprex combined with Tarceva (erlotinib) in lung cancer patients without the EGF receptor mutation or patients who have failed Tarceva therapy will initiate later this year.