Therapeutics: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL); nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB; NF

In vitro and mouse studies suggest TRAIL plus inhibition of either NF-κB, miR-21, miR-30c or miR-100 could help treat TRAIL-resistant lung cancer. Levels of NF-κB, miR-21, miR-30c and miR-100 were higher in TRAIL-resistant human cancer cell lines than in TRAIL-sensitive cell lines. Also in the resistant cells, knockdown of either NF-κB or any one of the three microRNAs decreased proliferation compared with normal expression of NF-κB and the miRNAs. In a mouse model of TRAIL-resistant xenograft lung cancer, TRAIL plus an NF-κB inhibitor decreased tumor volume more than the NF-κB inhibitor alone. Next steps include knocking down miR-21, miR-30c and miR-100 in combination with TRAIL administration in a mouse model of lung cancer.

Reata Pharmaceuticals Inc. has RTA 408 capsules that indirectly inhibit NF-κB in Phase I testing to treat non-small cell lung cancer (NSCLC). ...