Combining a NF-κB Inhibitor & TRAIL May Benefit NSCLC Patients

New research is suggesting that combining a NF-κB inhibitor and TNF-related apoptosis-inducing ligand (TRAIL) may have the ability to help a large number of patients with non-small cell lung cancer (NSCLC).

TRAIL is a promising agent for the treatment of cancer; however, so far it has had little effect on the most common lung tumors. Now, new research from The University of Manchester is pointing toward a new way to deliver TRAIL to help a greater percentage of NSCLC patients.¹

NSCLC accounts for approximately 85% of all lung cancer cases. The British researchers have found that a small RNA molecule called miR-148a is suppressed in TRAIL resistant cells. However, when TRAIL is combined with miR-148a, it sensitizes tumor cells to TRAIL and results in the tumor shrinking.^{2, 3}

TRAIL has been shown to induce apoptosis in malignant cells without causing significant toxicity in normal cells. However, investigators have been disappointed that only a very small subset of NSCLC patients respond to it. Finding out why this occurs may remove a major hurdle.

“Discovering a potential reason why TRAIL is resisted by lung cancer could lead us to new treatments for this particularly deadly form of the disease,” said lead study investigator Michela Garofalo, PhD, from the Cancer Research UK Manchester Institute, Manchester, England. “The miR-148a certainly seems to play a role in this resistance, so it’s an avenue to explore alongside other factors which influence how the tumors respond to treatment.”

Dr. Garofalo and her team have discovered that TRAIL increases the supply of a protein called NF-κB, which is a protein in resistant lung tumors. By suppressing NF-κB in cells, they found that TRAIL became much more effective at causing tumor cells to die.

“TRAIL is currently in clinical trials for other cancer types,” added Dr. Garofalo. “But little is known about why non-small cell lung cancer is so resistant. These findings begin to shed light on those unique reasons, and suggest that by inhibiting the factors that cause resistance, TRAIL might become a useful treatment.”

TRAIL-based approaches to several tumor types are now showing considerable promise, and the British researchers are now optimistic that these new findings will lead to advances in a better understanding of NSCLC as well as other cancers.

References:

• The University of Manchester News. (2015). Overcoming why a new treatment is resisted by lung cancer.
• Joshi P, Jeon YJ, Lagana A, et al. (2015). MicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC. Proceedings of the National Academy of Sciences of the United States of America.
• Jeon YJ, Middleton J, Kim T, et al. (2015). A set of NF-κB–regulated microRNAs induces acquired TRAIL resistance in Lung cancer.