A research group in the United States has found that genetic modification of the gene NRF2 sensitizes tumor cells to drug treatment, providing insight for future development of lung cancer treatment strategies.
Lung cancer remains a leader in cancer-related deaths. According to The Cancer Atlas, “lung cancer is responsible for nearly one in five cancer deaths worldwide (19.4% of all cancer deaths).” Although the development of this cancer is often preventable, the mortality rate is fairly high. This high mortality rate is largely due to how difficult it is to treat lung cancer.
Lung tumor cells are known to rapidly develop ways to evade chemotherapy, which can make it difficult for doctors to provide a treatment strategy. Now, Bialk and colleagues aim to use genomic editing to understand mechanisms that sensitize cancerous cells to these drugs, hoping to inform the design of future lung cancer treatment. They published their results in the journal Molecular Therapy: Oncolytics.
In this study, researchers genetically modified a gene, NRF2, commonly associated with the ability of lung tumors to evade drug treatment. This was achieved using the gene-editing tool CRISPR in a cultured lung cancer cell line. Researchers found that cells with modified NRF2 grew significantly slower when treated with common anti-tumor drugs. Moreover, when these modified cells were injected into mice, the growth of tumors was dramatically decreased. This growth was even further inhibited when combined with chemotherapy treatment in mice.
While this study adds important information to just how important this gene is in the ability of lung tumors to evade treatments, there is still a long way to translate these findings into clinical practice. There is currently very limited information on how CRISPR gene editing technology could be used as treatment in humans. Moreover, the experiments performed in this report are limited to cultured cells and artificial tumors in mice. Future experiments in lung cancer mouse models where the tumor is located in the lung would be important to bring these ideas closer clinical relevance in humans.
Nonetheless, this study represents an important advance in understanding lung cancer treatment. It utilizes gene editing to reveal new ways that we can target lung tumor cells to stop their rapid growth. Moreover, they find that targeted genetic modification can be combined with chemotherapy as a powerful inhibitor of tumor growth. The ideas and results in this study provide a foundation for future development of lung cancer treatment.
Written by Stacey Aggarwal, PhD
- PawelBialk,Yichen Wang, Kelly Banas, and Eric B. Kmiec. “Functional Gene Knockout of NRF2IncreasesChemosensitivity of Human Lung Cancer A549Cells In Vitro and in a Xenograft Mouse Model.” Molecular Therapy: Oncolytics. 2018.
- The Cancer Atlas. “Lung cancer.” American Cancer Society. Accessed 19 Dec 2018. http://canceratlas.cancer.org/the-burden/lung-cancer/