June 12 (UPI) — An experimental drug prevents a vital metabolic process in lung cancer cells’ growth and survival from occurring, according to lung treatment trials.
The drug was developed from concept to clinical trial by the University of Texas MD Anderson Cancer Center’s Institute for Applied Cancer Science and the Center for Co-Clinical Trials. The Houston researchers published their findings Monday in the journal Nature Medicine in two papers — one on preclinical work and another that described the drug’s potential for treatment of lung cancers with specific epigenetic alteration.
“Through this collaborative 18-month process, we identified and rapidly advanced IACS-10759 as the molecule for clinical development,” Dr. Emilia Di Francesco, associate director of Medicinal Chemistry at IACS, said in a press release. “We believe IACS-10759 will provide a promising new therapy for cancer patients.”
Cancer cells evolve to rely on two key metabolic processes, glycolysis and oxidative phosphorylation, or OXPHOS, to support growth and survival.
Researchers have focused on glycolysis for theropeutical uses while OXPHOS has remained largely unexplored. Researchers said there was an incomplete understanding of tumor contexts in which OXPHOS is essential.
“Through a comprehensive translational effort enabled by collaboration across MD Anderson, we have identified multiple cancers that are highly dependent on OXPHOS,” Dr. Joseph Marszalek, head of Translational Biology for CCCT, said.
More than 25 scientists on the Therapeutics Discovery team discovered and developed IACS-10759 as a potent and selective inhibitor of OXPHOS.
After pre-clinical research, an ongoing first-in-human Phase I clinical trial was launched in October 2016. A second Phase I trial in solid tumor indications began in November 2017.
IACS-10759 was tested for treating lung cancers harboring mutations in the SMARCA4 gene. It depends on OXPHOS for survival. SMARCA4 is part of a chromatin-modeling complex called SWI/SNF.
The study team found SMARCA4 mutant cells have enhanced oxygen consumption and increased respiratory capacity, making them susceptible to an OXPHOS inhibitor like IACS-10759.
“Our findings provide the mechanistic basis for further development of OXPHOS inhibitors as therapeutics against cancers with SWI/SNF-mutant tumors,” Dr. Lissanu Deribe, an instructor of genomic medicine, said. “Through multidisciplinary studies of new agents like IACS-10759, we aim to accelerate the availability of enhanced therapies for our patients.”