New Advances in Lung Cancer Research: SMACing Down Tumor Progression


Illustration of lung cancer An investigational class of drugs in combination with radiation therapy may improve immune function in patients.

Novel advances in the treatment of lung cancer have emerged from a new preclinical study from researchers at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC), published in the journal Clinical Cancer Research.

The study, led by Bo Lu, MD, PhD, Professor and Director of the Division of Molecular Radiation Biology, presents compelling evidence that an investigational class of drugs termed SMACs (secondary mitochondrial-derived activators of caspases) can effectively synergize with radiation treatment to improve lung cancer treatment outcomes. SMACs work by enhancing the cellular process of cell death, which plays numerous important roles in normal human development, tissue maintenance, and cancer progression.

These new findings demonstrate that SMACs can work together with ablative radiation therapy, which is widely used to treat early-stage non-small cell lung cancer. Ablative radiation therapy may be effective against microscopic cancer metastases through activation of anti-tumor immunity in the host as a consequence of self-vaccination by the ablated tumor cells, leading to survival rates that rival those of surgical treatment approaches. Other studies have shown that SMACs are also linked to similar effects on the immune system, leading the investigators to speculate that combining ablative radiation therapy and SMAC treatment might produce even more beneficial treatment effects for lung cancer patients.

To test this idea, Lu and colleagues utilized a mouse model of lung cancer to evaluate the effects of combining radiation therapy and SMAC treatment. They found that this combined treatment approach improved several measures of immune function in the mice and was associated with a dramatic delay in tumor growth compared to treatment with ablative radiation therapy alone. Most promisingly, some mice even exhibited a complete response, in which tumors were eliminated, and these mice were even able to fight off attempts to regrow the tumor.

“Our studies demonstrate that targeting the universal cell death mechanism can strongly enhance radiation-induced anti-lung cancer immunity, and this novel combinatorial treatment paradigm might prove applicable to a broad spectrum of human cancers,” said Lu. In terms of future directions, he noted that a research priority will be to further examine the molecular mechanism whereby SMACs enhance the immune response, while a translational priority will be to initiate early clinical trials to test the safety and efficacy of the combination of SMAC treatment together with ablative radiation therapy in human patients with lung cancer.